Abstract: Present study aimed to find the clinicopathological significance of PgR and its association with TP expression in colorectal cancer. Immunohistochemical studies were performed on 83 colorectal adenocarcinoma patients using corresponding monoclonal antibodies of PgR and TP and LSAB detection kit. Mucin producing cells showed PgR expression and its expression was detected in 15.6% of normal and 59% of malignant tissues. Significant association were observed between PgR negative expression in malignant tissues and larger tumor size (p = 0.006), higher incidence of secondary organ metastasis (p = 0.014) and tumor pathological stage (p = 0.041). A close association was observed between PgR and lack of TP expression in malignant tissues that means out of 49 PgR (+) tumors, 43 cases (86%) were TP negative (p = 0.046). It seems that tumors with better prognosis were more likely to express PgR in their malignant tissues, which affects the expression of TP as one of the major therapeutic targets in CRC. Present study suggests progesterone therapy as a possible effective strategy to suppress colorectal cancers and as a novel anti-angiogenic therapy for tumor dormancy which needs complimentary studies for confirmation.