A 62-year-old woman with newly diagnosed systemic AL amyloidosis was evaluated for severely increased left ventricular (LV) wall thickness. Her echocardiographic, cardiac MRI, and genetic findings led to a diagnosis of hypertrophic cardiomyopathy (HCM). Five years after achieving relative a partial hematologic response with chemotherapy, the patient died after developing rapidly progressive heart failure and cardiogenic shock. A full autopsy diagnosed both cardiac amyloidosis and HCM. The overlapping phenotypes of these two diseases resulted in a clinical diagnostic dilemma. This case highlights the importance of tissue diagnosis and genetic analysis in the evaluation of LV wall thickening when conflicting clinical features suggest divergent diagnoses.