Pterygium is a common degenerative disease characterized by fibrovascular outgrowth towards cornea. Around 200 million people have been reported to be affected by the pterygium in the world. Although the risk factors for pterygium are well documented, the molecular pathogenesis of pterygium seems to be very complex and remains highly elusive. However, the common sense for the development of pterygium appears to be deregulation of growth hemostasis due to aberrant apoptosis. In addition, pterygium shares many features with human cancers, including dysregulation of apoptosis, persistent proliferation, inflammation, invasion, and relapse following resection. Cytochrome P450 (CYP) monooxygenases are a superfamily of heme-containing enzymes with a wide range of structural and functional diversity. In the present study, we aimed to identify significant expression signatures of CYP gene in pterygium. For the study, a total number of 45 patients (30 primary and 15 recurrent pterygium) were included. For the high-throughput screening of CYP gene expression, Fluidigm 96.96 Dynamic Array Expression Chip was used and analyzed with BioMark™ HD System Real-Time PCR system. Remarkably, CYP genes were identified to be significantly overexpressed in both primary and recurrent pterygium samples. Most prominent overexpression was observed in CYP1A1, CYP11B2 and CYP4F2 in primary pterygium and CYP11A1 and CYP11B2 in recurrent pterygium. Consequently, present findings suggest the significant involvement of CYP genes in the development and progression of pterygium.