The predictive value of the route of venous drainage on prognosis was investigated in a consecutive series of 44 patients who underwent curative resection of pulmonary metastases from colorectal carcinoma. The primary tumor was located in the colon in 14 patients and in the upper third of the rectum in 11 patients, thus indicating blood drainage directed toward the portal vein (Group I). In 10 and 9 cases, respectively, the initial growth was in the middle and lower thirds of the rectum with the venous outflow at least partially directed into the vena cava (Group II). There was no obvious difference between the two groups regarding the initial site of cancer relapse. The liver was involved in 4 of 15 patients failing in Group I as opposed to 4 of 13 patients with hematogenous relapse in Group II. Median survival and tumor-free survival times were significantly longer in patients in Group I (58.4 and 50.2 months) than in patients in Group II (30.9 and 16.8 months), and, even more pronounced, in colon cancer patients (75.4 and 60.2 months) when compared with rectal cancer patients (31.0 and 17.9 months). In contrast, survival curves did not differ significantly if either the two groups with different routes of drainage (5-year survival 53 percent vs. 38 percent, 5-year tumor-free survival 43 percent vs. 37 percent), or tumors of the colon and rectum (5-year survival 67 percent vs. 38 percent, 5-year tumor-free survival 60 percent vs. 32 percent) were compared using the log-rank test. Similar trends were obtained for the subgroup of 34 patients without previous or simultaneous extrapulmonary recurrent disease at the time of lung resection. The primary tumor site does therefore not become a major criterion in selecting patients for surgical resection.