Carpal tunnel syndrome is the most common compression syndrome of a peripheral nerve. It mostly affects patients older than 50 years. One cause for a carpal tunnel syndrome is transthyretin (ATTR) amyloid, which deposits in the carpal tunnel tissue. Carpal tunnel syndrome can be the first symptom of ATTR amyloidosis, which in the worst case leads to amyloid cardiomyopathy with the symptoms of heart failure with reduction in quality and time of life. For this article, all histological tissue samples of carpal tunnel tissue, collected from 2010 to 2018, were evaluated according to age and gender of each patient. Evaluation of the ATTR amyloid content in different regions of the carpal tunnel has enabled a recommendation for resection for optimal histological diagnosis.In the Amyloid Registry Kiel, all cases are archived according to type of amyloid and available tissue. We evaluated 582 resected tissue samples of patients with ATTR amyloid in the carpal tunnel, collected from 2010 to the beginning of 2018. In addition, amyloid load of two different regions of the carpal tunnel (synovial tissue and tissue of the flexor retinaculum) were compared.The majority of resections came from women (53 %). The median age was 78 years for the entire collective, 77 years for men and 79 years for women. Specimens of the flexor retinaculum contained significantly more amyloid (9.66 % amyloid) than specimens of the synovial tissue (2.10 % amyloid). The prevalence of ATTR amyloid in carpal tunnel syndrome is 11.66 %.Both men and women develop a carpal tunnel syndrome caused by ATTR amyloid. In particular, at the age of over 50 years, amyloid deposits should be considered in the context of the etiological clarification of the carpal tunnel syndrome. Early histological diagnosis is highly relevant to identify the risk of cardiac amyloidosis. For an early and correct diagnosis of ATTR amyloidosis, histological examination of the flexor retinaculum is particularly necessary, and a sample excision should always be obtained and examined histologically.