Triple-hit lymphoma is a rare but serious form of Non-Hodgkin’s lymphoma that is known to have a worse prognosis than diffuse large B-cell lymphoma (DLBCL) or Burkitt lymphoma (BL) alone, with a survival time of only a few months. A triple-hit lymphoma has cytogenetic abnormalities consistent with chromosomal rearrangements of the BCL-6, BCL-2, and c-MYC genes, with MYC translocations having a worse prognosis. This specific type of lymphoma is medically challenging to treat, as standard chemotherapy is often ineffective. We report a case of a 47-year-old African American male with triple-hit lymphoma as a result of a series of progressive malignant transformations over a time course of three years.