Leukemic cell growth in SCID mice has been reported as a predictor of disease relapse. However, there is a paucity of literature regarding xenograft growth and clinical outcomes in non-small cell lung cancer (NSCLC). Seventy-nine specimens from patients with NSCLC were either subcutaneously implanted into SCID mice and/or placed in tissue culture. Retrospective chart review was correlated with stage, histology, necrosis, disease-free interval, and survival. Tumor xenografts were successfully established with 17 of 37 (46%) tumor biopsy tissues. Thirteen of 59 (22%) specimens grew in cell culture. Patients whose tumors grew in SCID mice had no difference in survival compared to those with no growth ( n=20, p=0.42). Median survival was 36 months in 13 patients whose tumors grew in cell culture compared to 39 months in 46 patients without growth. Eight of 12 (67%) patients with metastasis showed SCID/human xenograft growth, whereas nine of 25 (36%) without metastases did so ( p=0.08). Growth of tumor cells in vitro occurred in 11 of 31 (35%) adenocarcinomas, one of 25 (4%) squamous cell carcinomas, and one of three (33%) large cell carcinomas ( p=0.02). Well or moderately differentiated tumors grew in cell culture in only two of 22 (9%), whereas poorly or undifferentiated tumors grew in 11 of 32 (34%) cases ( p=0.03). We conclude that neither the ability of a tumor to engraft and grow in SCID mice nor its ability to grow in vitro in cell culture is a reliable predictor of disease outcome or survival in patients with NSCLC. The ability to propagate tumors in vitro appears to be more dependent upon the histological type of tumor and its degree of differentiation.