Materials and methods The authors report a study of the liquid of 144 hepatic non-neoplastic cysts: 52 untreated hydatid cysts (HC), 48 congenital non-parasitic cysts (nphc), 32 treated hydatid cysts (tHC) and 12 pseudocysts-bilomas (psc). Through echoguided method, the cystic liquid was subjected to the following investigations: evaluation of the macroscopic appearance, determination of the concentrations of glucose, nitrogen, sodium, potassium, chlorine, calcium, bilirubin, proteins and LDH, and parasitological and cytological evaluations of the sediment. Aim of this survey was to understand if the metabolites, enzymes, proteins and sediment of the cystic fluid have different concentrations in these hepatic cystic pathologies, to permit a differential diagnosis when the imaging and serology do not enable a certain diagnosis. Conclusions This study indicates that sampling of the liquid of non-neoplastic cysts of the liver can add information for a correct diagnosis of non-parasitic cysts, hydatid cysts and pseudocysts. In hydatid cysts, it can be used to evaluate the response to therapy.