Invasive protozoan infection with ameboma formation is relatively rare in advanced‑modern countries and can be mistakenly diagnosed as a neoplasm, which constitutes the majority of conditions in medical centers. The treatment between rectal ameboma and carcinoma is different, in which the former can be treated by effective medication, and the latter may sustain invasively inconvertible surgical intervention. Herein, we present a case of a 66‑year‑old man with a travel history to Japan who presented with anal pain and diarrhea secondary to ulcerative rectal mass detected by colonoscopy, which resembled colorectal carcinoma. The mass lesion was later determined histopathologically to be amebic infection caused by invasive Entamoeba histolytica, which had remarkable regression after metronidazole therapy. This case highlights the necessity of complete recognition of ulcerative rectal mass before definitive treatment and inadvertent clues from travel history to achieve a good outcome.