In this case, the importance of multiple myeloma in differential diagnosis of non-specific symptoms, such as macroglossia and significant pretibial edema, is highlighted. A 44-year-old male presented to the internal medicine outpatient clinic with complaints of ongoing and increasing enlargement of the tongue, difficulty in swallowing, and swelling of legs, all of which had been occurring for 6 months. In the CT scan, significant symmetrical enlargement of the tongue was detected. Making a pre-diagnosis of amyloidosis, a biopsy of the tongue was performed, but the results did not suggest amyloidosis. A rectal biopsy was therefore subsequently performed, and this time the results showed amyloid accumulation. Findings from the transthoracic echocardiography showed an ejection fraction of 48%, contrast hypertrophy in the left ventricle, Grade 3 diastolic dysfunction, 15–19 ml of pericardial fluid around the heart, and mild mitral failure. Taking into consideration the pathological and cardiologic findings, the patient was diagnosed with amyloidosis. Bearing in mind the possible relation between primary hematologic malignancy and amyloidosis, a bone marrow aspiration and a bone marrow biopsy were performed. From the results of the biopsy and aspiration of bone marrow, the patient was diagnosed with multiple myeloma and treatment plans were made accordingly. However, as the patient was in the process of undergoing treatment he died due to the development of cardiopulmonary failure