We described heterozygous deletion of tumor protein 53 (TP53) gene in 11 patients including 2 patients with non- malignant diseases (pneumonia) and 9 patients with malignant diseases [including small cell lung cancer (n = 3), non-small cell lung carcinoma (n = 4), non-Hodgkin's lymphoma (n= 1), and gastric carcinoma (n= 1)]. Chromosomal aberrant status was analyzed by fluorescence in situ hybridization with centromere specific and 17p13.1 locus specific probes. In 3 of 9 cancer patients we did not find malignant pleural effusion with histological examination and/or closed pleural biopsy. Heterozygous deletion of TP53 gene was found to be significantly higher in patients with malignant disease when compared to the patients with benign pleural fluid. As a result, we suggest that heterozygous deletion of TP53 may have indicator value for malignancy; however further studies are warranted to confirm this suggestion in large patient cohorts.