Molecular cytopathology is a rapidly evolving field of cytopathology that provides biological information about the response to personalised therapy and about the prognosis of neoplasms diagnosed on cytological samples. Biomarkers such as circulating tumour cells and circulating tumour DNA are increasingly being evaluated in blood and in other body fluids. Such liquid biopsies are non-invasive, repeatable, and feasible also in patients with severe comorbidities. However, liquid biopsy may be challenging due to a low concentration of biomarkers. In such cases, biomarkers can be detected with highly sensitive molecular techniques, which in turn should be validated and integrated in a complex algorithm that includes tissue-based molecular assessments. The aim of this review is to provide the cytopathologist with practical information that is relevant to daily practice, particularly regarding the emerging role of circulating tumour cells in the field of predictive molecular pathology.

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