The neuroendocrine [amine precursor uptake (decarboxylase)] properties of small (oat) cell lung cancer (SCC) have suggested that this neoplasm may have a separate histogensis from the other major types of human lung tumors. We now report that a key element of this concept, L-dopa decarboxylase activity, is present in surgical and autopsy tissues from all forms of lung cancer. Values are highest in SCC lesions; however, lung adenocarcinoma tissues can have considerable activity, and values overlap those for SCC and fall between values for SCC and large cell and squamous cell carcinoma. The distribution of diamine oxidase activity is identical except that even more overlap occurs between the major tumor types. These data may provide further evidence that SCC and other human lung cancers could share a common origin in the bronchial mucosa. In cell cuture, the distribution of the two enzyme activities is different. The average L-dopa decarboxylase activity is much higher (seven separate culture lines) than in the in vivo specimens, and it completely separates these cell lines from non-SCC lung tumors (four lines). Diamine oxidase is generally low in both SCC cells and non-SCC cells in culture and does not separate the various cell types. L-Dopa decarboxylase activity thus does appear to be a valuabe marker for separating SCC cells from other lung cancer cells in vitro.