We identified 126 tumor cell lines established from patients with small cell cancer at the NCI-Navy Medical Oncology Branch from 1977 through 1992. Extensive clinical information was available on 96 patients from whom these cell lines were established. These patients comprised approximately one fourth of the 407 patients treated on prospective therapeutic clinical trials during the same time period. The proportion of tumor cell lines established from previously untreated patients with both limited and extensive stage small cell lung cancer increased during the 16 years of the study (P = 0.008). MYC family DNA amplification was present in 16 of 44 (36%) tumor cell lines established from previously treated patients compared to 7 of 52 (11%) of tumor cell lines established from untreated patients (P = 0.009). MYC DNA amplification in tumor cell lines established from patients previously treated with chemotherapy continued to be associated with shortened survival (P = 0.001). The initiation of a policy to obtain tumor tissue for the purpose of selecting chemotherapeutic agents given to individual patients was associated with an increase in the proportion of patients from whom tumor cell lines could be established for both extensive and limited stage patients (P = 0.0001 and 0.05, respectively).