Why cannot I cast my COM object to the interface it implements in C#?

This exception can be a DLL Hell problem. But the simplest explanation is for what's missing from your snippet. Your Main() method is missing the [STAThread] attribute.

That's an important attribute that matters when you use COM objects in your code. Most of them are not thread-safe and they require a thread that's a hospitable home for code that cannot support threading. The attribute forces the state of the thread, the one you can set explicitly with Thread.SetApartmentState(). Which you can't do for the main thread of an app since Windows starts it, so the attribute is used to configure it.

If you omit it then you the main thread joins the MTA, the multi-threaded apartment. COM is then forced to create a new thread to give the component a safe home. Which requires all calls to be marshaled from your main thread to that helper thread. The E_NOINTERFACE error is raised when COM cannot find a way to do that, it requires a helper that knows how to serialize the method arguments. That's something that needs to be taken care of by the COM developer, he didn't do that. Sloppy but not unusual.

A requirement of an STA thread is that it also pumps a message loop. The kind you get in a Winforms or WPF app from Application.Run(). You don't have one in your code. You might get away with it since you don't actually make any calls from a worker thread. But COM components tend to rely on the message loop to be available for their own use. You'll notice this by it misbehaving, not raising an event or deadlocking.

So start fixing this by applying the attribute first:

[STAThread]
static void Main(string[] args)
{
    // etc..
}

Which will solve this exception. If you have the described event raising or deadlock problems then you'll need to change your application type. Winforms is usually easy to get going.

I cannot otherwise take a stab at the mocking failure. There are significant deployment details involved with COM, registry keys have to be written to allow COM to discover components. You have to get the guids right and the interfaces have to be an exact match. Regasm.exe is required to register a .NET component that's [ComVisible]. If you try to mock an existing COM component, and got it right, then you'll destroy the registration for the real component. Not so sure that's worth pursuing ;) And you'll have a significant problem adding a reference to the [ComVisible] assembly, the IDE refuses to allow a .NET program to use a .NET assembly through COM. Only late binding can fool the machine. Judging from the COM exception, you haven't gotten close to mocking yet. Best to use the COM component as-is, also a real test.

So, the problem was that my DLL with IDiagnostics interface was generated from a TLB, and that TLB never got registered.

Since the DLL was imported from the TLB, RegAsm.exe refuses to register the library. So I used the regtlibv12.exe tool to register the TLB itself:

C:\Windows\Microsoft.NET\Framework\v4.0.30319\regtlibv12.exe "$(ProjectDir)\lib\Diagnostics.tlb"

Then everything magically started to work.

Since regtlibv12 is not a supported tool, I still don't know how to do this properly.