A massive adaptive radiation on the Hawaiian archipelago has produced approximately one-quarter of the fly species in the family Drosophilidae. The Hawaiian Drosophila clade has long been recognized as a model system for the study of both the ecology of island endemics and the evolution of developmental mechanisms, but relatively few genomic and transcriptomic datasets are available for this group. We present here a differential expression analysis of the transcriptional profiles of two highly conserved embryonic stages in the Hawaiian picture-wing fly Drosophila grimshawi. When we compared our results to previously published datasets across the family Drosophilidae, we identified cases of both gains and losses of gene representation in D. grimshawi, including an apparent delay in Hox gene activation. We also found a high expression of unannotated genes. Most transcripts of unannotated genes with open reading frames do not have identified homologs in non-Hawaiian Drosophila species, although the vast majority have sequence matches in genomes of other Hawaiian picture-wing flies. Some of these unannotated genes may have arisen from noncoding sequence in the ancestor of Hawaiian flies or during the evolution of the clade. Our results suggest that both the modified use of ancestral genes and the evolution of new ones may occur in rapid radiations.