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Marjolin's ulcers have a grave prognosis, especially when regional nodes are involved. Recent studies suggest such cancers are in an immunologically privileged sites due to the dense scar tissue. The prognosis has been shown to be much worse for tumors not having a round cell infiltrate prior to surgery, as in Marjolin's ulcers. The use of topical 5-fluorouracil (5-FU) induces a round cell infiltrate. Three case reports of large Marjolin's ulcers are presented which were first treated with topical 5-FU. Radical ablative surgery was avoided in these patients with a successful outcome.