BACKGROUND Carcinoid tumors of the gastrointestinal tract differ in their clinical and histopathologic features, depending on the site of origin. There are few clinicopathologic studies that specifically describe jejunoileal carcinoid tumors. METHODS One hundred sixty-seven ileal and jejunal carcinoids were retrospectively studied with emphasis on clinical, pathologic, immunohistochemical, and prognostic features. RESULTS The mean age of patients at the time of presentation was 62 +/- 12 years (range, 13-93 years). Eight patients had carcinoid syndrome (5%) and 1 had Zollinger-Ellison syndrome. Twenty-six percent of tumors were multiple, and 77% were transmurally invasive; 31% had regional lymph node metastases only, and 32% had liver or mesenteric metastases. Ninety-three percent of tumors had an insular growth pattern. Serotonin was expressed in 86% of tumors (86 of 102), chromogranin in 92%, and neuron specific enolase in 95%. Twenty percent of tumors (10 of 51) expressed prostatic acid phosphatase; 96% were argyrophil, and 98% argentaffin. Of 80 cases with follow-up data (mean follow-up, 52 +/- 5 months), 21% were dead of disease, 16% were dead of other causes, 19% were alive with disease, and 44% had no evidence of disease at last follow-up. The 5-year Kaplan-Meier survival estimate for all cases was 58%. By univariate analysis, survival was negatively correlated with distant metastases at the time of surgery (P = 0.002), mitotic rate (P = 0.01), tumor multiplicity (P = 0.01), the presence of carcinoid syndrome (P = 0.02), depth of invasion (P = 0.03), and female gender (P = 0.05); by multivariate analysis, survival was negatively associated with distant metastasis (P = 0.002), carcinoid syndrome (P = 0.01), and female gender (P = 0.03). CONCLUSIONS Jejunoileal carcinoid tumors have a relatively high rate of transmural invasion and aggressive clinical behavior. They are usually insular and largely argentaffin, with a high rate of chromogranin and serotonin positivity. These features differentiate jejunoileal carcinoids from other gastrointestinal carcinoids.