: Despite good advancements for diagnosis and treatment, cancer is still a big threat to our society. 10 million new cases are diagnosed along with 6 million deaths every year. Keeping in view the existence of diverse pattern of cancer occurrence, this study explored the histopathological spectrum of malignancies in tertiary care center in Western Maharashtra. To evaluate the spectrum of malignant lesions in various organs and to study their demographic profile and histopathological features. To evaluate the trend and epidemiological patterns of cancer among patients. This is a combined retrospective and prospective study that included 735 patient specimens obtained either post-surgically or through biopsy. The specimens were evaluated based on site, histopathological features and tumor differentiation. Most of the patients are middle to old age groups. Female were slightly higher in number at 50.07% compared to males at 49.93%. Most common histopathological type of carcinoma included squamous cell carcinoma at 41.22%, followed by adenocarcinoma at 23.54%, infiltrating ductal carcinoma at 19.59%. Most common site of tumors was located at head and neck area at 26.39%, followed by breast carcinoma at 19.6%. Among GIT cancers, esophageal involvement was noted in 5.71%. Bladder cancers accounted for 4.0% whereas kidney cancers accounted for 4.63% of all cancers. In cancers of female genital tract, cervical cancers, ovarian & adnexal tumors, vulval & vaginal tumors accounted for 7.07%, 0.27%, 0.14% respectively. Among cancers of male genital tract, prostate and penis tumors accounted for 10.07%, 1.63% respectively. In our study, majority of tumors were located at head and neck area accounted for 26.39% followed by breast carcinoma at 19.86%. The study showed prevailing epidemiological profile of cancers in Western Maharashtra. Appropriate screening measures can be directed keeping in mind most prevalent cancers and mitigation measures can be taken accordingly..