The protein tyrosine phosphatase gamma (PTP gamma) gene has recently been suggested as a candidate tumor suppressor gene involved in the oncogenesis of human lung and renal cancers, although no direct evidence for PTP gamma mutations has been demonstrated thus far. We explored the status of PTP gamma in 31 human lung cancer cell lines as well as in various other types of human tumor cell lines. Northern blot analysis revealed that two independent cell lines expressed PTP gamma mRNAs with sizes distinct from those in human fetal and adult normal lung. However, our extensive search for mutations in the PTP gamma gene failed to identify any abnormalities in the cytoplasmic region, which contains two protein tyrosine phosphatase-like domains. These results warrant further examination of genetic alterations in the extracellular and transmembrane domains of PTP gamma, which had not been cloned at the time of the present study.