The AIDs-related fungal pathogen Pneumocystis carinii is unusual in having a remarkably compact genome of 7.7 megabase pairs (mbp) whose small size presents the opportunity to identify the essential eukaryotic core of genes. The essential eukaryotic core is defined to be a collection of essential genes shared by all eukaryotes. Sequencing the 3′ ends of more than 5500 cDNAs from P. carinii allowed us to identify about 200 genes shared with its nearest known but distant relative, Schizosaccharomyces pombe and also Saccharomyces cerevisiae, and with homologs known to be essential in S. pombe or S. cerevisae. As the cDNA library contains about one half of the P. carinii genes, the size of the essential eukaryotic core (∼400) is slightly larger than the prokaryotic core (265–350) being identified by studies of the bacterial pathogen Mycoplasma genitalium. The collection of genes in the essential eukaryotic core may prove useful in identifying new broad spectrum antifungal drug targets.