The diagnostic and prognostic implications of p53 immunostaining have been investigated in 59 pulmonary neuroendocrine tumors, including typical carcinoids (n = 15), so-called "atypical carcinoids" (n = 22), and small cell lung carcinomas (SCLCs; n = 22). Immunocytochemistry was performed on formalin-fixed, paraffin-embedded samples using the monoclonal antibody PAb1801, which has been shown to be suitable for staining fixed and embedded tissue sections. p53 immunoreactivity was restricted to atypical carcinoids (45% of the cases being immunoreactive) and to SCLCs (which were positively stained in 59% of the cases), whereas it was consistently lacking in typical carcinoid tumors. When the group of the so-called "atypical carcinoids" was further reclassified, p53 immunostaining was strictly confined to those cases belonging to the histologically more aggressive subsets (well differentiated neuroendocrine carcinoma subsets II and III). Within the same tumor type, however, p53 immunoreactivity did not correlate with the clinical outcome of the disease and was not predictive of the length of survival. The data indicate that abnormal p53 expression (which is strictly dependent on structural abnormalities of the p53 gene) is detectable in the majority of neuroendocrine carcinomas of the lung and might represent a useful adjunct in the differential diagnosis of pulmonary neuroendocrine neoplasms, particularly in routinely fixed and embedded small bronchoscopic biopsies.