<h4>Background</h4>Transthyretin amyloid cardiomyopathy (TTR-CM) is a form of nonischemic cardiomyopathy associated with progressive heart failure, persistent symptoms, and reduced quality of life despite advances in medical therapy.<h4>Case summary</h4>We present a man with TTR-CM and heart failure with reduced ejection fraction who remained severely symptomatic despite guideline-directed medical therapy, cardiac resynchronization therapy, and atrial fibrillation ablation. Here, TTR is linked to cutaneous mastocytosis.