Pescadillo is a multifunctional, nuclear protein involved in rRNA precursor processing, ribosomal assembly, and transcriptional regulation. Pescadillo has been assigned important functions in embryonic development and tumor formation. We previously identified pescadillo as a potential downstream target of non-canonical Wnt-4 signaling. Here we have investigated for the first time the function of the Xenopus laevis homolog of pescadillo during early embryogenesis on a molecular level. Loss of function analysis indicates that pescadillo is required for eye development and neural crest migration. BrdU incorporation and TUNEL assays indicate that a loss of pescadillo function affects proliferation and triggers apoptosis through a p53-mediated mechanism. Furthermore, pescadillo affects the expression of early eye-specific marker genes, likely independent of its function in regulating proliferation and apoptosis, and in addition migration of cranial neural crest cells. Our data indicate that pescadillo has multiple important functions during X. laevis development and that its function is highly conserved among different species.