The diagnosis of amyloidosis is important for early intervention, disease monitoring, and prevention of complications and progression. Carpal tunnel syndrome (CTS) and trigger digit (TD) are two common conditions associated with early disease. The purpose of this study was to define disease prevalence among patients with bilateral CTS and multiple TDs and assess for an increased rate of diagnosis in the presence of both. Men older than 50 years and women older than 60 years of age diagnosed with bilateral CTS, multiple TDs, or a combination of the 2 were prospectively enrolled in our study. Tenosynovial biopsy samples taken at the time of surgery were tested for the presence of amyloid using Congo red staining. Demographic and medical covariates were also collected and analyzed for differences between amyloid-positive and -negative patients. Fifty-six patients were enrolled in the study, and nine patients tested positive for amyloid deposition. The demographics and medical comorbidities were similar between amyloid-positive and -negative patients. Thirty patients with bilateral CTS were enrolled, and four tested positive for amyloid. For patients with multiple TDs, a total of 17 patients were enrolled, and 4 tested positive for amyloid. Among patients with multiple TDs, only men tested positive for amyloid and were, on average, younger than those who tested negative (61 and 73 years, respectively). Patients presenting with a combination of CTS and TD did not exhibit increased amyloid discovery. Hand surgeons should consider tenosynovial biopsy in men older than 50 years and women older than 60 years presenting with either bilateral CTS or multiple TDs. Prognostic IV.