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• Early mesothelioma diagnosis is challenging, especially on cytology. • Pleural effusions offer a useful resource of mesothelial cells for diagnosis. • BAP1 and CDKN2A losses are diagnostically relevant molecular alterations. • IHC and FISH improve diagnosis in all sample types but need validation. • Analysis of gene expression profiles may improve diagnosis. Pathology plays an important role in diagnosing mesothelioma since radiological and clinical findings alone cannot distinguish mesothelioma reliably from its many mimics. The long-held gold standard for pathological diagnosis requires a tissue biopsy that, in addition to mesothelial phenotype, demonstrates invasion, but this is challenged by the WHO recognition of mesothelioma in situ (MIS) and concurrent acknowledgement of all mesotheliomas as malignant. Tumor sampling and ancillary techniques are of paramount importance for diagnosis of MIS. Standardisation of these techniques, cut-off points and terminology, and an updated staging system are urgently required. These clinically relevant issues and the impact of new developments were illustrated at the pathology session of 15th meeting of the International Mesothelioma Interest Group. It was reported that combination of losses in p16 nuclear expression, with cut-off ≤ 1%, and cytoplasmic MTAP with cut-off ≥ 30% demonstrated increased specificity (96%) and high sensitivity (86%) for CDKN2A HD detection. Otherwise, the combination of p16 IHC and CDKN2A HD may improve prognosis. The potential usefulness of pleural effusions for early diagnosis was demonstrated in a retrospective study investigating pleural effusions had been diagnosed as benign prior to mesothelioma diagnosis. Alterations of BAP1 (IHC) and CDKN2A (FISH) were detectable 2 or more years prior diagnosis. Moreover, analysis of gene expression profiles in cytology samples by principal component analysis discriminated reactive hyperpasia from epitheliod mesothelioma. Early diagnosis, including cytology diagnosis, is being acyively investigated. Since no treatment recommendations exist for MIS, pathologists recognise the need for international collaborations to fully characterise this rare entity. Clear communication with the clinical teams is required to ensure optimum patient care. The data reported in this meeting are encouraging and open avenues for further work that will allow even earlier diagnosis and better characterisation of mesothelioma progression, based on changes in gene expression, including epigenetic changes. [ABSTRACT FROM AUTHOR]