During mitosis of multiple types of precursor cells in Drosophila, Numb is asymmetrically distributed between the two daughter cells and confers distinct daughter cell fates. Here we report the identification of a novel gene product, Partner of Numb (PON), based on its physical interaction with Numb. PON is asymmetrically localized during mitosis and colocalizes with Numb. Loss of pon function disrupts Numb localization in muscle progenitors and delays Numb crescent formation in neural precursors. Moreover, ectopically expressed PON responds to the apical-basal polarity of epithelial cells and is sufficient to localize Numb basally. We propose that PON is one component of a multimolecular machinery that localizes Numb by responding to polarity cues conserved in neural precursors and epithelial cells.