Although all carcinoids are potentially malignant, their biologic behavior is quite variable. Currently there are no reliable morphological criteria to predict metastatic potential. Cell adhesion molecules, such as CD44 and E-cadherin, are considered important in regulating invasion and metastasis of tumors. Also, angiogenesis has been shown to be associated with tumor growth and progression. In this study, we examined 51 carcinoids, including 13 carcinoids with known lymph node and/or visceral metastasis, for expression of CD44s (the standard form of CD44) and E-cadherin by immunohistochemistry. We found that 55% and 37% of carcinoids were negative for CD44s and E-cadherin, respectively. Carcinoids with lymph node and/or visceral metastasis were significantly more frequently negative for CD44s than were those without demonstrated metastasis (P =.030). Ten of 11 tumors with lymph node metastasis lacked CD44s (P =.022), whereas E-cadherin was negative in only 3 (P =.975). Additionally, we analyzed microvessel density to evaluate the role of tumor angiogenesis in the tumor behavior. Carcinoid tumors in general demonstrated high microvessel density (160 +/- 82/five 200x fields), irrespective of location and with and without metastasis. These results suggest that loss of CD44s, but not E-cadherin, may be a useful predictor of metastatic potential of carcinoid tumors.