The aim of this study was to determine the incidence and role of c-erbB-2 overexpression as a predictive/prognostic marker in small-cell lung carcinoma (SCLC). We performed a retrospective study on subjects with a biopsy-proven diagnosis of SCLC. A chart review for demographic and clinical data was performed on patients with SCLC diagnosed between 1998 and 2004. c-erbB-2 overexpression was evaluated using immunohistochemistry performed on archival paraffin-embedded specimens. Sixty-seven patients with SCLC were identified (6 females, 61 males; median age- 56.5 yr, range-34-75) all of whom had adequate tissue specimens available for c-erB-2 testing. Of the 67 specimens, 12 (17.9%) showed c-erbB-2 overexpression. Seventy-five of the cases were positive for c-erbB-2, had extensive disease. The median overall survival of patients with SCLC whose tumors were positive and negative for c-erbB-2 were 8 +/- 0.9 months (95%CI 6.3-9.7) and 11 +/- 1.5 months (95%CI 8.0-14.0), respectively. c-erbB-2 overexpression detected using immunohistochemistry is observed in 17.9% of patients with SCLC and has statistically significant prognostic value. Our findings suggest that c-erbB-2 may be a potential target for site-specific immunotherapy in SCLC. Considering one technique examined, further molecular investigation is needed to confirm these preliminary findings.