The genetic mechanisms underlying the progression to the metastatic phenotype of lung cancer are poorly understood. We recently showed that small cell lung cancer (SCLC) and metastasizing squamous cell carcinomas are characterized by an increased incidence of allelic loss on chromosome 10q. In the present study we performed a deletion mapping using 24 polymorphic markers on chromosome 10q22-q26 in 39 squamous cell carcinomas (SCC) of the lung identifying 14 metastatic carcinomas (74%) and three non-metastatic SCC (15%) with allelic imbalance. The allelotype analysis indicated three regions of allelic loss that were clustered at the loci Afm086/D10S541, D10S185 and D10S1782/D10S169. A localized microsatellite instability was observed in two carcinomas for the markers D10S1686 and D10S1782. In addition the PTEN/MMAC1 gene was analysed by direct DNA sequencing and Southern blot analysis in 25 and 28 carcinomas, respectively, without detecting any genomic alterations. Similarly, no altered transcript was detected in 15 tumor cell lines and 20 primary tumors by Northern blot analysis or RT-PCR. In summary, three distinct regions of allelic imbalance were identified suggesting that multiple tumor suppressor genes on chromosome 10q contribute to tumor progression and metastases formation of lung cancer.