Have to rewatch it, too. Can we go make a list of those things.

It looks like a lipstick mark to me.  I think it's clearer when he's standing up looking at the text message.   Also, it's not there in the scene just before Irene kisses him (although I know that's mind palace) and appears immediately after. 

I didn't notice it on first viewing either!

Yeah, I only saw it the 3rd time or so.
But I'm quite sure it is a lipsick mark.

The thing-I-didn't-notice-first-time-around that has blown me away the most, is the scene in The Sign of Three when Sherlock is talking to all the Mayfly Man's victims on several laptops at once, and John interrupts him with questions. When I read a (tumblr?) post that it is actually Sherlock's Mind Palace representation of John (the real John was wearing different clothes), I was amazed I hadn't noticed it myself, even after several rewatches.

I've missed this as well. Maybe my brain just figured it was a bruise or a mark from John's 'assault' or Irene's riding crop. 

Interesting though! 

This definitely makes sense.

There are two possibilities: she came before the boys came back and the mark is indeed a bruise, or she came trough the open window.

There is another thing about that scene that struck me: 
Irene drugs Sherlock, leaves her house via the window. Sherlock goes into his MP/drug trance whatever and solves the hiker case, leading Irene through it. He falls back into his imaginary bed, Irene comes into his real bedroom, puts the coat back, kisses him, disappears. 

So we have a fluent passage from a drug state/mind palace scene to a real scene and we never see where one ends and the other begins. I find it very interesting how early Moftiss have started these things, building them up until the culmination in TAB. 
 

I imagined Irene came and left via the window, as she's shown she's skilled at those things.  And we know she was there because (apart from the lipstick mark), there's the coat and altered ringtone on the phone.  I think that she talks to him, and Sherlock visualises it in his dream/mind palace.   John probably didn't notice because he was in the living room (down a corridor) and the flat is on a busy road.  Perhaps he had the TV on.  We don't hear him, either.