A cell can divide asymmetrically by specifically segregating a determinant into one of its daughter cells. The Numb protein is a candidate for such a determinant in the asymmetric cell divisions of the developing Drosophila nervous system. Numb is a membrane-associated protein that localizes asymmetrically during cell division and segregates into one daughter cell, where it is required for the specification of the correct cell fate. Here we show that a nuclear protein, Prospero, translocates to the membrane at the beginning of cell division and colocalizes with Numb throughout mitosis, suggesting a common mechanism for asymmetric segregation. Numb and Prospero localization is coupled to mitosis and tightly correlated with the position of one of the two centrosomes. In contrast to centrosome positioning, however, Numb and Prospero localization is independent of microtubules. Cytochalasin D treatment suggests that the process is also independent of actin. We propose that there is an organizer of asymmetric cell division which provides positional information for both the orientation of the mitotic spindle and asymmetric localization of Numb and Prospero.