There is a peptide sequence homology between the gene product of human MUC4 and rat Muc4/sialomucin complex (SMC). Each contains a transmembrane subunit with two epidermal growth factor (EGF)-like domains that act as ligand for ErbB2. MUC4 and ErbB2 mediate intracellular signaling pathways that are linked to repression of apoptosis and either to proliferation or to differentiation of tumor cells. This study investigates the expression of human MUC4 in neoplastic and corresponding non-neoplastic tissues, and the relation of MUC4 expression in neoplastic tissues to ErbB2 expression, apoptosis, proliferation, differentiation, and tumor stage in a series of 100 non-small cell lung carcinomas (NSCLCs). MUC4 and ErbB2 expressions and cell proliferation (PCNA) were shown using immunohistochemistry. Apoptotic index (AI) and tumor differentiation were determined by morphologic criteria. All the non-neoplastic bronchial tissues and 85% of NSCLCs showed MUC4 expression. MUC4 expression was found to be higher in neoplastic than in non-neoplastic tissues (Yates correction p: 0.0006). MUC4 expression was inversely correlated with AI (p=0.0002) and was correlated with ErbB2 expression (p=0.022), but not with PCNA counts and tumor stage. Our results indirectly suggest that MUC4, in association with ErbB-2, might be involved in the repression of apoptosis and differentiation rather than proliferation in tumor cells of NSCLCs.