In Ghana, majority of cancer studies have focused on only two main teaching hospitals. However, there is the need to study the disease burden from other parts of the country. This study was designed to review cancer cases recorded in major hospitals in the Volta Region of Ghana, with the aim of determining the incidence of cancers and cancer-related mortalities, and contribute to cancer data in the country. In-patient diagnosis data from 2012 to 2014 were collected from 21 hospitals in the Volta Region of Ghana. The data were entered and structured in Microsoft Excel and analyzed with IBM SPSS Statistics 20 and GraphPad Prism 6. Cervical, breast, liver, soft tissue, and prostate cancer were identified as the commonly diagnosed cancers in the Region. Socioeconomic factors such as poor educational background and occupation were associated with incidence of cancer in the study area. The incidence of cancer was determined to be approximately 9, 11, and 6 morbidities per 100,000 people in the years 2012, 2013, and 2014, respectively, with liver cancer being the leading cause of deaths. Public awareness and screening efforts are thus needed to fight against cancer in the Volta Region, and Ghana as a whole. In addition, this study is an original report of cancers in the Volta Region of Ghana and underscores the need to report ethnic/population-specific frequencies to effectively evaluate the burden of cancer in the country. Impact statement Region-specific cancer reports are essential in knowing the common cancers in specific populations. This study reports all cancer types recorded in the major hospitals in the Volta Region of Ghana, a population that is sparsely captured in the national cancer registries. The study identified the common cancers as well as the death rates in the Volta Region, hence contributing to the national effort to report cancer data. Although not comprising all the elements of a cancer registry, our data will augment the effort of the two national cancer registries in Ghana to provide the national cancer reports.