PURPOSE: Many patients with amyloidosis undergo carpal tunnel release (CTR) before amyloidosis diagnosis and before developing cardiac or other serious disease manifestations. The purposes of this study were to examine if our patient population had a similar prevalence of positive amyloidosis diagnoses to that in prior studies and to describe the results of implementing a screening program for amyloidosis. METHODS: We retrospectively reviewed the biopsy results and subsequent interventions for all patients who underwent screening tenosynovial biopsy during CTR from March 2020 through December 2021. Amyloid screening was offered to patients who met the criteria for increased risk of disease using an appropriateness screening algorithm. RESULTS: Seventy-five (48%) of 156 patients who underwent CTR met the eligibility criteria for amyloidosis testing. Of the 62 patients who agreed to undergo tenosynovial biopsy, 14 had amyloid-positive biopsy specimens (10 men and 4 women). All patients with positive tenosynovial biopsies had bilateral carpal tunnel syndrome and wild-type transthyretin amyloid subtype. One patient was diagnosed and started treatment for otherwise asymptomatic cardiac amyloidosis. CONCLUSIONS: The incidence of amyloid-positive tenosynovial biopsy results from CTR was 22.5% in patients using the criteria from an appropriateness screening algorithm, which was higher than previously reported. Implementation of a screening program for patients undergoing CTR requires a multidisciplinary approach and may result in early diagnosis and lifesaving interventions for patients with amyloidosis. TYPE OF STUDY/LEVEL OF EVIDENCE: Differential diagnosis/symptom prevalence study, II.