The organisers of the Florida-based event issued a statement confirming the news and reassuring fans about the Spider-Man co-creator's health.
"I regret to announce that Stan Lee has cancelled his appearance at MegaCon 2013. We received the call late last night. He is okay, but is taking a small break from doing convention appearances," read a statement on the convention's Facebook page.
Former Marvel Comics president Lee has now cancelled two convention appearances in many weeks after bowing out of Amazing Arizona Comic Con due to illness.
Concerns over the 90-year-old's health emerged last year when Lee cancelled a string of expo appearances. He later revealed that he had undergone pace-maker surgery.
MegaCon takes place in Orlando, Florida between March 15 and 17.