Breast cancer is ranked the top in types of cancer that affects internationally. It affects up to 1 in 13 women during their lifetime. Physiotherapy is one of the major sources of recovery in patients of Mastectomy in terms of pain, ranges, and function. OBJECTIVE: To compare the effects of pre-operative shoulder rehabilitation program versus post-operative mastectomy patients. METHODS: This was a randomized clinical trial. The study setting was Oncology Department, Mayo Hospital Lahore, Shokat Khanum and Gulab Devi Hospital Lahore. The study was completed in 6 months. Total 50 subjects were allocated in two groups using lottery method of randomization. Patient with age less than 40 years, diagnosed with breast cancer were included, while those with associated signs of musculoskeletal problems, autoimmune systemic disease and advanced medical problem was excluded. Group A received set of exercises comprised of range of motion exercises and lymph edema education pre and post operatively. Group B received post rehabilitation exercises only. Data was analyzed by SPSS 16.0. Independent t test was applied to analyze between group differences and paired sample t test to see within group improvement. Descriptive statistics was in form of mean, variance and appropriate graphs. RESULTS: Independent sample test results regarding post interventional disability of arm, shoulder, and hand (DASH) score showed significant p value 0.000 with a mean difference of 23.28000 while assuming equal variances. The mean and standard deviation of pain score was 3.76 (SD+0.778) pre/post combination group and post-operative rehabilitation program alone 4.1200 (SD+0.78102) with a statistically equal improvement in both groups (0.109). CONCLUSION: The study concluded that there was significant difference with better outcomes in terms of improvement in function, pain and range in patients having combination protocol i.e. pre-operative and post-operative rehab protocol in patient of mastectomy as compared to post-operative rehabilitation protocol alone.