Secondary tumors of the gastrointestinal (GI) tract are unusual but are probably more common than clinically suspected. Comparison of surgical pathologic findings and autopsy experience over a 14-yr period revealed a different spectrum of tumors, which may reflect clinical practice issues and the pathophysiology of individual tumors. Seventy-three surgical resection or biopsy cases with clinically evident secondary tumors were compared with 108 autopsy cases with secondary malignancies involving the GI tract. The most common tumors in surgical specimens were melanoma (22 cases), ovary (11 cases), bladder (eight cases), breast (six cases), and lung (five cases). The most common primary tumors at autopsy were lung (21 cases), gynecologic malignancies (18 cases), breast (14 cases), and pancreas (nine cases). In most cases, routine histologic examination yielded clues to the primary tumor. Metastatic breast carcinoma cases had a high potential for misinterpretation because most metastases consisted of infiltrating strands of pleomorphic cells without gland formation. Signet ring cells were present in most metastases (all six surgical cases and seven of 14 autopsies), regardless of the histologic type of the primary breast carcinoma. The time from diagnosis of the primary tumor to development of GI involvement varied widely, from presentation with GI metastases to more than 30 yr for metastatic malignant melanoma. Survival after development of GI involvement was generally poor, with most patients surviving less than 1 yr. However, long-term palliation may be achieved in a small subset of patients, chiefly those with single small bowel deposits of malignant melanoma or patients with breast carcinoma responsive to tamoxifen.