Ovarian cancer presents as disseminated disease in the majority of cases. Tumor metastasis to the peritoneal and/or pleural cavity is evident in two-thirds of cases at diagnosis and relapse is most often detected at this anatomic site. Despite the fact that the primary tumor is amenable to surgical removal in the majority of cases, ovarian cancer research, including the evaluation of therapeutic targets, has concentrated on primary disease. In recent years, we analyzed the site-dependent expression of cancer-associated and regulatory molecules in primary tumors, effusions and solid metastases. Our data show that some molecules (e.g., Ets transcription factors) are expressed at all anatomic sites in ovarian carcinoma and that their expression in primary and metastatic disease is associated with poor prognosis. However, the majority of molecules (e.g., cadherins, integrins, and nerve growth factor receptors) are differentially expressed along tumor progression and have different prognostic value depending on the organ sampled. Specifically, cancer-associated molecules with a well-characterized clinical significance in solid tumors (e.g., matrix metalloproteinases) have no such role in effusions. Finally, a growing number of molecules are differentially expressed in primary diagnosis (pre-chemotherapy) and disease recurrence (post-chemotherapy) specimens, reflecting the effect of disease progression and chemotherapy. This review will present the current knowledge in this area.