Empty follicle syndrome (EFS) is characterized by the absence of oocytes after apparently normal follicular development and the pathogenesis of this syndrome is not well characterized. The aim of this study was to analyse whole gene expression of granulosa cells (GC) from a patient with recurrent EFS by using Affymetrix GeneChip. A total of 160 genes were identified as being differentially expressed (by at least two-fold) between EFS GC and the control GC. Most of the differentially expressed genes were involved in cell growth and death. Among these were MAPK3, which plays an important role in the inhibition of apoptosis, was down-regulated 2.3-fold in EFS GC. Moreover, secretory phospholipase A2 and transforming growth factor receptor II, key regulators of cell death pathway, were down-regulated 3.54- and 2.82-fold respectively in EFS. Gene expression of granulosa cells from the EFS patient was significantly altered. The absence of the oocytes might be due to the increased apoptotic gene expression and the reduction of transcripts whose products are responsible for healthy follicular growth. Gene expression analyses might be a useful technique in identifying markers to follow a healthy follicular maturation and understanding the events that lead to EFS.