Introduction <p>Gastrointestinal symptoms resulting from amyloid deposition can differ significantly and might be mistaken for other prevalent intestinal disorders, complicating the diagnostic process. Here, we present a case of systemic amyloidosis with gastrointestinal involvement, where the primary symptom of the disease is gastrointestinal issues.</p> Case presentation <p>A 63-year-old Iranian man presented with intermittent diarrhea, diffuse abdominal pain, and fatigue. The muscle strength of the lower limbs was 2/5, whereas that of the upper limbs was 4/5. Cardiac consultation was requested owing to electrocardiogram changes that were compatible with infiltrative cardiomyopathy. Esophagogastroduodenoscopy revealed multiple clean-based ulcers in the antrum. Four-limb electromyography and nerve conduction velocity was performed, leading to a diagnosis of chronic, partially active axonal-dominant type polyradiculoneuropathy. Owing to the involvement of various organs, particularly the heart, peripheral nervous system, and kidneys, we performed a biopsy of the abdominal fat pad owing to suspected amyloidosis.</p> Conclusion <p>Amyloidosis is a disease with many different manifestations. Although it may not be common, it can present a diagnostic challenge for clinicians, especially when gastrointestinal symptoms are pronounced.</p>