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Effusion draining is a minimally invasive procedure with few complications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>We performed a review of publications regarding the use of molecular testing in serous effusions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In diagnostics, BAP\u20101 IHC and CDKN2A FISH are powerful tools for the diagnosis of malignant mesothelioma. FISH, PCR, and EBER\u2010ISH work well in lymphomas. RT\u2010PCR may enhance the diagnosis of secondary epithelial malignancies. In theranostics, molecular testing on serous effusions is widely reported for the detection of alterations in genes related to lung carcinomas, such as EGFR, ALK, ROS1, and BRAF. PD\u2010L1 expression testing by immunohistochemistry (IHC) also seems to be viable in this type of sample. HER2 FISH and IHC provide actionable results in the context of breast malignancies. Results in serous effusions seem to be equivalent to tissue biopsies for most applications and across different molecular techniques. The most interesting technology is next\u2010generation sequencing (NGS), given its ability to sequence multiple genes on a single sample and the decreasing costs that have closely followed increasing throughputs. Cell\u2010free DNA from effusion supernatants might be the most promising area for future research, showing superiority to serum and even to cell\u2010block samples in limited studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Molecular tests are viable in serous effusion specimens when sufficient material is available. 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