Abstract Introduction/Objective The co-occurrence of acute myeloid leukemia (AML) and multiple myeloma (MM) presents a diagnostic challenge, particularly when it arises without prior chemotherapy exposure. This study aims to elucidate the clinical characteristics, diagnostic approach, and management implications of such synchronous hematologic malignancies through a detailed case report. Methods/Case Report A 64-year-old female with no previous medical history presented with chest pain, shortness of breath, and hematologic abnormalities. Clinical evaluation revealed severe pancytopenia, cystic liver mass, enlarged retroperitoneal lymph nodes, and hypercalcemia. Peripheral blood smear indicated hematologic malignancy, prompting further investigation. Bone marrow aspirate analysis, including flow cytometry and immunohistochemical stains, was performed to confirm the dual cell populations of AML blasts and MM plasma cells. Results (if a Case Study enter NA) Flow cytometric analysis and immunohistochemical stains of the bone marrow aspirate confirmed the presence of distinct cell populations: blasts expressing markers consistent with AML and abundant plasma cells indicative of MM. Monotypism of plasma cells was established, with kappa predominance. Notably, there was no coexpression of markers between the AML blasts and MM plasma cells. Conclusion This case highlights the rare occurrence of synchronous AML and MM in a patient without prior chemotherapy exposure. The diagnostic approach involving flow cytometry and immunohistochemical stains proved essential in confirming the dual hematologic malignancies. Clinicians should be vigilant for such presentations, as timely diagnosis and appropriate management are crucial for optimizing patient outcomes in these complex cases.