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1.
When you need a tissue, but don't have one on your person, which then causes an issue
I almost had a tissue issue but i had a tissue in my pocket and therefore there was no issue.
by gutter-ball j January 31, 2008
 
2.
The perplexing conundrums that arise from leaving evidence of a recent masturbation session laying about.
Conrad: Holy crap! We've got to go back to the apartment before Pam wakes up, I forgot I left a bunch of used kleenex by the computer!
Farnsworth: Hey, your tissue issues aren't going to make me late to work, Sgt. Spank-o-tron!
by Mr. Softey February 03, 2009
 
3.
A human resource issue when someone is whining and a mock tissue to wipe the eye is necessary.

Also a human resource issue involving people rather than equipment or processes.
Are you whining? This sounds like a tissue issue.

We've got another tissue issue, the warehouse crew is bitching again.
by C. Wright May 10, 2005