AIMS: Sentinel lymph node (SLN) status is the most important prognostic factor in intermediate thickness melanoma. The amount of metastatic disease in positive SLNs varies greatly between patients, and this tumour burden appears to influence the prognosis of node-positive patients. The aim was to use objective stereological techniques to correlate accurately total SLN tumour burden with recurrence and patient survival. METHODS AND RESULTS: SLNs from 327 patients were examined by complete step sectioning and immunohistochemistry. The total metastasis volume (TMV) of 156 positive SLNs from 99 patients (30.3%) was measured using stereological methods based on the 2D-nucleator and Cavalieri's principle. The maximum metastasis diameter was also measured. These two measurements were correlated with disease recurrence and patient survival. The mean TMV for SLN+ patients was 10.5 mm(3) (median 0.05 mm(3); range 0.0001-623.7 mm(3)). Median follow-up was 26.3 months. On multivariate analysis, TMV was an independent predictor of recurrence when corrected for primary tumour thickness (P = 0.001) and was a stronger prognosticator compared with the maximum metastasis diameter (P < 0.0001 versus P = 0.01). CONCLUSIONS: Combining total step sectioning of SLNs with stereological assessment of metastases, we found metastasis volume to be a highly significant predictor of disease recurrence and survival.