Objectives: Our aims were (1) to compare the respective ability of ultrasonography and palpation to detect nodal metastasis during initial staging and follow-up in patients having melanomas and (2) to assess, we believe for the first time, which ultrasound criteria should be used to define metastasis in cases of cutaneous or mucosal melanoma. Design: Prospective single-center study. Nodal metastasis was confirmed by histopathologic evaluation. Setting: Dermatology and radiology departments of a university hospital. Patients: A total of 160 new consecutive patients with stage I to stage III melanoma. Intervention: Experienced operators independently performed 391 paired palpation and ultrasonographic examinations. Main Outcome Measures: Firm enlarged nodes found on palpation were considered metastatic. On ultrasonographic examination, circular or oval hypoechoic lymph nodes lacking hyperechoic hila were considered metastatic (stringent criteria). Nodes with 2 or fewer of these patterns and other published signs of metastasis (ie, intranodal nodular hypoechoic focus and irregularity of the node margin) were considered suspicious. Results: Over the 6-year study period 33 patients developed nodal metastasis. For palpation and ultrasonography using the stringent criteria, respectively, sensitivity was 41.5% (95% confidence interval 95% CI , 29.6-53.5) and 76.9% (95% CI, 66.7% -87.2% ) (P < .001)and specificity was 95.7% (95% CI, 93.5% -97.9% ) and 98.4% (95% CI, 97.1% -99.8% ) (P < .05). Including ultrasonographically suspicious lymph nodes significantly lowered specificity (86.2% 95% CI, 82.5-89.9 ) (P < .05) without improving sensitivity. Previous lymphadenectomy had little impact on ultrasonographic findings. Conclusion: Ultrasonography using stringent criteria of nodal metastasis, which are easy to identify and reliable, is superior to palpation for early detection of regional lymph node metastases of melanoma. Objectives: Our aims were (1) to compare the respective ability of ultrasonography and palpation to detect nodal metastasis during initial staging and follow-up in patients having melanomas and (2) to assess, we believe for the first time, which ultrasound criteria should be used to define metastasis in cases of cutaneous or mucosal melanoma. Design: Prospective single-center study. Settings: Dermatology and radiology departments of a university hospital. Patients: A total of 160 new consecutive patients with stage I to stage III melanoma. Intervention: Experienced operators independently performed 391 paired palpation and ultrasonographic examinations. Main Outcome Measures: Firm enlarged nodes found on palpation were considered metastatic. On ultrasonographic examination, circular or oval hypoechoic lymph nodes lacking hyperechoic hila were considered metastatic (stringent criteria). Nodes with 2 or fewer of these patterns and other published signs of metastasis (ie, intranodal nodular hypoechoic focus and irregularity of the node margin) were considered suspicious. Results: Over the 6-year study period 33 patients developed nodal metastasis. For palpation and ultrasonography using the stringent criteria, respectively, sensitivity was 41.5% (95% CI, 29.6-53.5) and 76.9% (95% CI, 66.7% -87.2%) (P <.001) and specificity was 95.7% (95% CI, 93.5% (95% CI, 97.1% -99.8%) (P <.05). Including ultrasonographically suspicious lymph node was significantly lower (86.2% 95% CI, 82.5-89.9) improving sensitivity. Previous lymphadenectomy had little impact on ultrasonographic findings. Conclusion: Ultrasonography using stringent criteria of nodal metastasis, which are easy to identify and reliable, is superior to palpation for early detection of regional lymph node metastases of melanoma.