Histopathological assessment of myxofibrosarcoma may be difficult, especially on the basis of a small core biopsy, which enables only a crude evaluation of grade and prognosis. We have tested the hypothesis that determination of cell cycle state may assist in the diagnostic assessment of myxofibrosarcoma. We have studied 51 cases of high-grade (n=20), intermediate-grade (n=21), and low-grade (n=10) myxofibrosarcomas, as well as nine cases of benign myxoma. Cell cycle state within tumors was determined by immunostaining for the recently described marker minichromosome maintenance protein 2 (MCM2), together with Ki67. Labelling indices for both markers were correlated with tumor grade, mitotic index, and time to first recurrence. The MCM2 labelling indices were significantly higher than the Ki-67 labelling indices. Both indices showed a significant correlation with the mitotic index and both showed significant increases with increasing grade of myxofibrosarcoma. The MCM2 labelling index (but not the Ki67 labelling index) showed a significant inverse exponential correlation with the time to first recurrence. Myxoid and cellular areas showed no difference in the MCM2 and Ki-67 labeling index, suggesting that clinically useful information could be obtained from any component of a myxofibrosarcoma sampled in a needle biopsy and/or cytological specimen. We therefore suggest that assessment of cell cycle state may be a useful diagnostic adjunct in the histopathological assessment of myxofibrosarcoma, by enabling more accurate determination of grade and prediction of outcome.