Colorectal cancer is one of the most common malignancy worldwide. Genetic instability may play an important role in the accumulation of the large amount of genetic alterations during the pathogenesis of cancer. There are two major forms of genetic instability in colorectal cancers that are chromosomal instability and microsatellit instability. We proposed to define P53 gene deletion in colorectal cancers by Flouresans in Sitis Hybridization (FISH). We analyzed available 14 tumoral tissue samples from 28 cases whose slides were performed using touch preparation protocol. Conventional cytogenetic examination were performed from 28 cases’ blood samples. Interphase FISH study is performed using P53 locus specific DNA probe and examined 500 cells for each patient. No change of P53 gene is observed 64% in patients. 7% of cases were obtained the gain of P53 gene and 29% of cases were obtained the allelic lose of P53 gene. We found statistically significant correlation between P53 gene change and cancer phases and between patient ages and P53 gene change by using Spearman Correlation Test. Interphase FISH is a powerful method which could establish gene deletions and gains in cancers. The relation between P53 gene deletion and colorectal cancer is not yet explained. For this reason, further examinations are needed to use of molecular genetic and immunohistochemical techniques in this subject.