Objective. The objective of this study was to determine whether clinicopathologic findings or the immunohistochemical presence of molecular markers are predictive of clinical outcome in patients with small cell carcinoma of the cervix (SCCC). Methods. A retrospective review of cases of carcinoma of the cervix was conducted to identify SCCC. From 1978 to 1999, 16 patients were identified at our institution with the diagnosis of SCCC. Microscopic sections of paraffin-embedded tissue specimens were evaluated for confirmation of diagnosis. Specimens were immunohistochemically stained with antibodies to three neuroendocrine markers: neuron-specific enolase, chromagranin (CGR), and synaptophysin. Specimens were also stained for protein expression of p53, erbB2, proliferating cell nuclear antigen, and c-myc. The relationship between molecular markers and clinical outcome was determined. Results. All 16 cases met the histologic criteria for SCCC. Fourteen of 16 tumors (88%) stained positive for neuroendocrine differentiation. Eleven of 16 patients (69%) died from disease with a median survival of 19 months; there were 3 long-term survivors (greater than 5 years). CGR was positive in 8 (50%) specimens and was found to be highly predictive of death (P = 0.001). Complete loss of p53 protein was seen in 8 patients, 7 of whom died with a median survival of 20 months. Conclusion. Immunohistochemistry can be helpful in confirming difficult cases of SCCC. Further studies are necessary to define molecular markers that may be predictive of outcome in patients with SCCC. © 2001 Academic Press.