In Ghana, breast cancer remains the most common cancer and the leading cause of cancer deaths among women. The cost of treating cancer is huge and poses a great challenge for patients, their families, and health care systems. While comprehensive studies have been conducted on the economic burden of cancers in developed economies such as the EU and the US, there are limited studies in Africa, and Ghana, in particular. This study quantitatively assessed Ghana's direct and indirect costs of breast cancer treatment. Primary data were collected using a questionnaire administered to 217 breast cancer patients at the Korle-Bu and Komfo Anokye Teaching Hospitals, Ghana's two leading hospitals, and Sweden Ghana Medical Centre. Direct and indirect costs were computed using the Cost-of-Illness Approach. Quantitative analysis was done using multivariate linear regression. The findings showed that the breast cancer patients studied paid a median amount of Ghana cedis (GHC) 31,021.0 (IQR; 25,262.5-42,147.0), approximating USD 5,500.2 (IQR: 4,477.0-7,469.2 USD) for their treatment within one year of active treatment in 2019. About 61.9% (95% CI: 61.8-62.0%) of this cost was direct cost, while the remaining 38.1% (95% CI: 38.0-38.1%) was indirect cost. Patients who sought care from public facilities for breast cancer paid a median amount of GHC 29,606.3 (USD 5,249.3), while those who sought care from private facilities paid GHC 55,071.2 (USD 9,744.4). Findings from the multivariate linear regression indicate that being married/cohabiting, divorced/separated and having tertiary level education predicted higher cost of breast cancer treatment while patients on retirement and patients in the middle stage (Stage II) of breast cancer diagnoses were associated with lower cost of breast cancer treatment. The cost of breast cancer treatment poses a significant burden on patients and their families. There is a need for increased public funding for breast cancer treatment to reduce the huge economic burden its treatment poses for patients and their families.