The Cavalieri volume estimator has been employed to determine the macroscopic tumor volume of 34 cutaneous malignant melanomas. With this rapid and unbiased method using histological specimens from slabs of known thickness, tumor volumes between 3.9 mm3 and 841.5 mm3 were found. The coefficient of error (CE) for tumor volumes ranged between 0.028 and 0.141, with a combined group CE of 0.043. There was a remarkably good correlation between tumor volume and maximal vertical tumor thickness estimated according to Breslow, with a correlation coefficient of r = 0.86 for all tumors, and of r = 0.82, if the one extremely big tumor is omitted. Both inter- and intraobserver variability was very low, with only ∼1-2% difference. Thus, the method described allows for the reproducible, rapid, and unbiased estimation of tumor volume independent of the shape of the tumor.