The added prognostic value of cellular DNA content compared with single and combined morphometric factors and classical parameters such as tumor size, nodal status, histologic grade and estrogen receptor (ER) content was investigated in 225 consecutive breast-cancer patients with long follow-up. Of all features investigated, the MPI (multivariate prognostic index) had the strongest prognostic value [Mantel-Cox (MC) = 48.2, p < 0.000051. The results further showed that neither age nor ER content had significant prognostic value, but the DNA index (DI) as a single parameter had (though weak) prognostic significance (MC = 5.9, p = 0.015); a similar result was obtained with the percentage of S-phase cells (MC = 6.1, p = 0.013). The DI had (restricted) additional prognostic value to the morphometric features MPI plus DI Mantel-Cox 53.0, p < 0.OOOl). The percentage of 5 -phase cells had no additional prognostic value over the MPI. On the other hand, the additional value of the DI over tumor size and nodal status was much more impressive (MC = 41 .O and 4 0 . 7 ) , although it did not reach the prognostic significance of the MPI. Prediction of disease outcome with a linear combination of quantitative microscopical parameters of the primary tumor alone [MA1 (mitotic activity index), DI and mean nuclear area] was very accurate, even without considering lymph-node status (MC 30.8, p < 0.0005). Grade had no additional value to the MPI at all (p = 0.76). This could be especially important for lymph-node-negative patients in whom the prognostic value of the MPI and the MA1 are confirmed. 3To whom reprint requests should be sent.