Peritoneal carcinomatosis is a major cause of surgical treatment failure in patients with colorectal cancer. In the past patients with this condition have had a lethal outcome. In this study, 64 consecutive patients were treated by the cytoreductive approach, which involved surgery to maximally resect all cancer in the abdomen and pelvis, early postoperative intraperitoneal chemotherapy with 5-fluorouracil (5-FU) and mitomycin C, and three cycles of adjuvant intraperitoneal 5-FU with systemic mitomycin C. The clinical features that may affect prognosis were assessed and critically analyzed statistically. Peritoneal implant size of < 5 cm present in the abdomen and pelvis at the time of exploration correlated with a good prognosis (p < 0.0001), as did complete cytoreduction with tumor removed to nodules < 2.5 mm (p < 0.0001). Involvement of only one or two of the five abdominopelvic regions, compared to three or more regions, was a significant determinant of prognosis (p < 0.0001). Finally, a mucinous histologic type correlated adversely with prognosis when compared to intestinal-type adenocarcinomas (p < 0.001). These data suggest that patients with small-volume peritoneal seeding from colon cancer should be treated with cytoreductive surgery and aggressive regional and systemic chemotherapy in an attempt to achieve long-term disease-free survival.