BACKGROUND Primary signet-ring cell carcinoma of the colon and rectum is a rare form of adenocarcinoma of the large intestine. The purpose of this study was to help better define the natural history of this entity. METHODS The medical records of 3,690 patients with colorectal cancer seen at The Roswell Park Cancer Institute between September 1971 and December 1993 were reviewed. We report on 29 patients with pathologic confirmation of primary signet-ring cell carcinoma. Patient demographics, clinical, and histologic parameters were evaluated. Survival was calculated by the Kaplan-Meier method. RESULTS There was a nearly equal distribution of primary signet-ring cell carcinoma between the right colon and left colon/rectum. In most cases the tumors were > 6 cm, ulcerated, and involved the full thickness of the bowel wall. Nodal or metastatic disease was present in 21 of 29 patients (72%) at the time of diagnosis. Four patients (14%) had synchronous colorectal adenocarcinomas. Twenty-two patients died of disease progression. At the time of death, two patients (9%) had failed in the liver, whereas all 22 patients had peritoneal carcinomatosis. CONCLUSIONS Patients with primary signet-ring cell colorectal carcinoma frequently present with late-stage disease. In 23 of 29 patients, the disease rapidly recurred or progressed. Peritoneal carcinomatosis is the most common pattern of failure.