Cytologic examination during endoscopic biopsy is a rapid, useful and reliable adjunct to mucosal biopsy for the diagnosis of lesions of GI tract. The study was conducted to assess the diagnostic value of squash cytology of biopsy samples and establish it as a primary diagnostic technique. It was a prospective study carried out in the Department of Pathology and Apex Diagnostic centre, Cuttack over a period of 2 years from August 2010 to July 2012. The first endoscopic biopsy specimen collected from GI lesions was crushed between two glass slides and fixed with 95% isopropyl alcohol. Smears were stained with H and E and papanicolaous' stain. 288 patients with GI lesions were subjected to endoscopic biopsy and squash cytology. Females were more commonly affected than males (M:F = 1:1.2) . 216 (75%) lesions were seen in stomach, out of which 45 (20%) were benign lesions. 50% of rectal lesions were malignant .Colonic lesions accounted for 6.25% and esophageal lesions were 6.25% of all GI lesions. All the cytologic evaluations were correlated with biopsy findings. A positive correlation was seen in 91% cases.Squash cytology is a quick, simple and inexpensive adjunct to endoscopic biopsy and does not require any additional equipment. It can be used as a necessary information to clinician for fast management of patients with GI lesions.