The anaphase promoting complex or cyclosome (APC/C) is a large protein complex with an ubiquitin ligase activity which specifically targets mitotic regulatory proteins for proteasomal degradation. The APC/C contains at least 11 subunits, most of which are evolutionarily conserved from yeasts to humans. We have isolated and characterized mutant alleles of the gene that codes for the APC10/Doc1 subunit of the Drosophila APC/C. Loss of function APC10/Doc1 mutants have rudimentary imaginal discs and arrest their development as prepupae. Larval neuroblasts from these mutants show gross mitotic defects including high mitotic index, chromosome overcondensation, metaphase-like arrest and frequent aneuploid and polyploid cells. Mitotically arrested cells accumulate one of the main substrates of APC/C, cyclin B, most likely due to disabled ubiquitination activity. Our results suggest that the Apc10/Doc1 subunit has an essential role in establishing E3 ubiquitin ligase activity of APC/C in Drosophila.