Many reports have been made concerning underlying and associated conditions causing pseudomembranous colitis and it has been documented that occurrence of pseudomembranous colitis is related with antibiotics administration. Recent study showed that Clostridium difficile produced enterotoxin by colonization in intestinal wall and leading into pseudomembranous colitis. Diagnosis is based on positive culture of Clostridium difficile, positive test of Clostridium difficile toxin and specific histological findings after observation of whitish plaque on colonoscopic or sigmoidoscopic examination. Authors have experienced one case of pseudomembranous colitis developing after long term ampicillin administration in a case with colon cancer associated with diarrhea and diagnosis was confirmed by typical pseudomembrane on biopsy following classical whitish plaque observation on sigmoidoscopic examination. Symptoms have been ameliorated by discontinuation of antibiotics and administration of metronidazole in four days and disappearance of whitish plaque on repeated sigmoidoscopic examination and improvement of clinical symptoms after 9 days of medication.