Although still considered relatively uncommon, the incidence of carcinoid tumors appears to be increasing at a more rapid rate than other cancers. Surgical treatment of carcinoid tumors of the gastrointestinal (GI) tract can be particularly difficult due to the intense fibrotic response; multiple growth factors and their receptors are suspected to be involved in this process yet this aspect has not been studied in detail. The purpose of our study was twofold: 1) to determine the incidence, patient and tumor characteristics, synchronicity, and outcome of patients with GI carcinoid tumors using the Surveillance, Epidemiology and End Results (SEER) database, and 2) to delineate the expression pattern of growth factor receptors in carcinoid tumors. METHODS. 1) The SEER database search, which is comprised of cancer incidence and survival data from cancer registries covering approximately 26% of the US population, provided information on patients diagnosed with carcinoid tumors from 1990-2002. 2) Paraffin-embedded blocks of carcinoid tumors (n = 45) from the foregut, midgut, and hindgut were sectioned and stained for the following growth factor receptors (GFRs): epidermal growth factor receptor (EGF-R), insulin-like growth factor receptor (IGF-R), vascular endothelial growth factor receptor (VEGF-R), HER-2/neu, and neural cell adhesion molecule (NCAM). RESULTS: 1) Over the 12 year analysis period, 18,180 patients were identified with carcinoid tumors of the foregut, midgut, and hindgut; the incidence of carcinoid tumors increased ~2-fold during this time period. The most common site of GI carcinoid was colorectal (28%), followed by the small intestine (20%), and stomach (6%). At the time of diagnosis 49%, 21%, and 23% of patients demonstrated localized disease, regional disease, and distant disease, respectively. A single synchronous lesion was noted in 17% of patients, and 3% had two synchronous lesions. The overall 5-year survival for patients was ~58%. 2) Of the patients with carcinoid tumors resected at our institution, there was a trend of increased expression of VEGF-R and IGF-R, particularly in the foregut and midgut carcinoids. CONCLUSIONS. Analysis of a large database representative of a comprehensive source of population-based information confirms that the incidence of carcinoid tumors is increasing with an approximate doubling in the number of carcinoid cases from 1990-2002. Furthermore, we demonstrate an increase in VEGF-R and IGF-R expression, particularly of- foregut carcinoids, suggesting that GFR inhibitors may be effective adjuvant therapy for carcinoid cancer and the associated fibrotic response.