The International System for serous fluids cytopathology is a cytologic classification which purpose is to establish a consensus on diagnostic terminology. The exponential discovery of prognostic and theranostic molecular alterations in many cancers, particularly in advanced stages, led the authors to describe the indications and the feasibility of these new markers on cytological samples from serous effusions. The various immunocytochemistry techniques, FISH and those testing DNA and RNA are reported in regard to their ability to identify the main targets currently explored in routine practice. The vast majority of these crucial markers can be reliably tested on effusion fluids. The International System for serous effusion fluids also includes a chapter dedicated to peritoneal washings and the application of the classification to this particular type of sample. The objective is to "wash" the peritoneal cavity with a saline solution to unfix cells from the cavity's wall and collect those that have previously naturally detached. This procedure, performed before surgery of tumors and before any manipulation, allows a cytological analysis that specifies the staging of gynecological and non-gynecological tumors and excludes occult malignant cells in the presence of tumors appearing benign.