General:
* Issue
* Difficulty
* Challenge
* Obstacle
* Trouble
* Dilemma
* Predicament
* Quandary
* Conundrum
* Snag
* Hitch
* Bottleneck
* Complication
* Crisis
* Situation
* Matter
Mathematical:
* Equation
* Inequality
* Theorem
* Proposition
* Lemma
* Puzzle
Computer Science:
* Bug
* Error
* Fault
* Glitch
* Issue
Other:
* Fault
* Defect
* Flaw
* Shortcoming
* Deficiency
* Weakness
* Drawback
The best synonym will depend on the specific context in which you are using the word "problem."