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Background: Patients who have pleural effusions typically undergo thoracentesis with examination of pleural fluid in their initial assessment. However, limited data are available on the diagnostic yield of pleural fluid bacterial cultures and fungal and acid-fast bacilli (AFB) smear and cultures in patients with cancer.Methods: We performed a retrospective cohort study of consecutive patients who had new onset pleural effusions and underwent an initial thoracentesis. The primary outcome was diagnostic yield of pleural fluid bacterial cultures and fungal and AFB smear and cultures.Results: Of 1637 patients, 1547 (94%) had evidence of active malignancy and 1359 (83%) had evidence of metastatic disease. Of the 1637 patients, 542 (33%) had high clinical suspicion of pneumonia within 14 days prior to thoracentesis. Only 14 patients (1.1%) had positive pleural fluid bacterial cultures, and only 6 of these positive cultures met the criteria for true pleural space infection.Conclusions: The incidence of positive results from pleural fluid bacterial, fungal, and AFB in cancer populations is very low. Unless there is a suspicion for infection, microbiological analysis should be ordered selectively. [ABSTRACT FROM AUTHOR]