Several times I have come across a bug in different Outlook versions when the “Signatures” button doesn’t work. No matter how many times you click it, the Signatures window won’t appear.
This time the bug appeared on Windows 10 with the newly installed RTM version of Outlook 2016. After clicking the Signatures button in the File -> Options -> Mail, nothing happened and the signature didn’t appear.
I tried to repair, remove and reinstall Office, cleanup the registry – but nothing helped. How to set a user Outlook signature in this case?

In one of the previous articles we told how to setup an Outlook signature based on user information from Active Directory. There we mentioned that in Windows 10, 8.1 and 7 the files with Outlook signatures are located in the user profile folder %APPDATA%\Microsoft\Signatures (C:\Users\username\AppData\Roaming\Microsoft\Signatures). So if you create an HTML/RTF/TXT file with the signature text and save it in the specified directory, you can insert your signature using the corresponding button in the Outlook 2016 interface when creating a new email or replying (Outlook must be restarted).
But it is quite inconvenient since each time you have to press the ‘Signature’ button manually. You can assign this file as a default Outlook signature through the registry. To do it, remove the First-Run parameter in registry key HKCU\Software\Microsoft\Office\<Office Version>\Outlook\Setup and create 2 string (REG_SZ) values: NewSignature and ReplySignature in the reg key HKEY_CURRENT_USER\Software\Microsoft\Office\16.0\Common\MailSettings (for Outlook 2016). Specify the full path to the signature file as the values of these parameters.
However, this fix is inconvenient and not flexible.
There is a description of a similar bug in Windows 10 on support.office.com. To solve the problem of the Signatures button that is not working, it is recommend to uninstall a modern app Microsoft Office Desktop App (Settings -> Apps -> Apps & Features).

If it hasn’t helped, I have found some opinions on technical forums that the signature issue often appears after mailbox migration to the another domain or on computers with the preinstalled Office.
In order to make the Signatures button work, try the following:
In these registry keys (for x64 and x86 Office editions respectively) change the values of the Default and LocalServer32 parameters to the full path to the outlook.exe executable file on your computer (for example, to C:\Program Files (x86)\Microsoft Office\Office16\Outlook.exe for Outlook 2016):
HKEY_LOCAL_MACHINE\SOFTWARE\Classes\Wow6432Node\CLSID\{0006F03A-0000-0000-C000-000000000046}\LocalServer32HKEY_LOCAL_MACHINE\SOFTWARE\Classes\CLSID\{0006F03A-0000-0000-C000-000000000046}\LocalServer32

If this method hasn’t helped, try to use this REG file (for Office 2016 and Office 365):
Windows Registry Editor Version 5.00
[HKEY_CLASSES_ROOT\Outlook.Application]
@="Microsoft Outlook 16.0 Object Library"
[HKEY_CLASSES_ROOT\Outlook.Application\CLSID]
@="{0006F03A-0000-0000-C000-000000000046}"
[HKEY_CLASSES_ROOT\Outlook.Application\CurVer]
@="Outlook.Application.16"
[HKEY_CLASSES_ROOT\Outlook.Application.16]
@="Microsoft Outlook 16.0 Object Library"
[HKEY_CLASSES_ROOT\Outlook.Application.16\CLSID]
@="{0006F03A-0000-0000-C000-000000000046}"
[HKEY_CLASSES_ROOT\Wow6432Node\CLSID\{0006F03A-0000-0000-C000-000000000046}]
[HKEY_CLASSES_ROOT\Wow6432Node\CLSID\{0006F03A-0000-0000-C000-000000000046}\InprocServer32]
"Assembly"="Microsoft.Office.Interop.Outlook, Version=16.0.0.0, Culture=neutral, PublicKeyToken=71E9BCE111E9429C"
"Class"="Microsoft.Office.Interop.Outlook.ApplicationClass"
"RuntimeVersion"="v2.0.50727"
[HKEY_CLASSES_ROOT\Wow6432Node\CLSID\{0006F03A-0000-0000-C000-000000000046}\InprocServer32\16.0.0.0]
"Assembly"="Microsoft.Office.Interop.Outlook, Version=16.0.0.0, Culture=neutral, PublicKeyToken=71E9BCE111E9429C"
"Class"="Microsoft.Office.Interop.Outlook.ApplicationClass"
"RuntimeVersion"="v2.0.50727"
[HKEY_CLASSES_ROOT\Wow6432Node\CLSID\{0006F03A-0000-0000-C000-000000000046}\LocalServer32]
@="C:\\Program Files\\Microsoft Office\\Office16\\OUTLOOK.EXE"
[HKEY_CLASSES_ROOT\Wow6432Node\CLSID\{0006F03A-0000-0000-C000-000000000046}\ProgID]
@="Outlook.Application.16"
[HKEY_CLASSES_ROOT\Wow6432Node\CLSID\{0006F03A-0000-0000-C000-000000000046}\Typelib]
@="{00062FFF-0000-0000-C000-000000000046}"
If signature problem occurs in Office 2010, replace 16 with 14; if in Outlook 2013, replace 16 with 15.