Abstract Purpose Symptomatic trapeziometacarpal arthrosis is primarily diagnosed on clinical grounds. The X-ray appearance correlates poorly with the presence and severity of pain; therefore, radiography is not a useful tool to define which patient is symptomatic, nor which one should be treated. There is not a specific gold standard test. The grind test is the most used clinical test; however, its level of diagnostic accuracy is not very high. The aim of this study is to describe and validate a new clinical test. Materials and Methods A prospective study was conducted to evaluate the diagnostic performance and reliability of the compression and flexion test. Results A total of 106 patients were included. Excellent interobserver agreement was found for both semiology tests (kappa = 0.82 and intraclass correlation coefficient = 0.97). The area under the curve for the compression and flexion test showed an estimate of 99.2 (95% confidence interval [CI]: 97.6–100) and for the grind test of 62 (95% CI: 51.2–71.9). The diagnostic performance of the compression and flexion test showed a sensitivity of 100% (95% CI: 92.1–99.9) and a specificity of 98.4% (95% CI: 91.2–100), in contrast to the grind test that reports a sensitivity of 22.2% (95% CI: 11.2–37.1) and a specificity of 93.4% [95% CI: 84.1–98.2]. Conclusions The diagnostic performance of the compression and flexion test is higher than that of the grind test. Furthermore, the results show an excellent interobserver correlation and diagnostic accuracy, making it a useful clinical tool for the diagnosis of trapeziometacarpal arthritis. Type of Study/Level of Evidence Diagnostic tests II.