Nuclear changes (micronuclei) in blood are a well-established biomarker of toxic injury and related genotoxicity in mussel, fish and humans, as well. Yet, the relationship between the frequencies of micronuclei in blood and nuclear changes in liver cells itself and the higher potential risk to develop liver cancer is not yet fully implemented. We analysed and diagnosed macroscopic liver changes in H&E and Feulgen stained histological liver sections (2 um of thickness) together with blood smears (stained with Sytox Green) from same individuals in flounder caught along a well-known contaminant gradient in the North Sea. Results showed an increase in micronuclei frequencies in blood at the more contaminated sites and higher frequencies of macroscopically visible neoplastic liver changes. Females tend to reveal more micronuclei than males in blood in concert with higher rates of liver cancer which is in line with our long term observations in the past 10 years.In the livers of same individuals nuclear changes were diagnosed in early to degenerative liver lesion, liver lesions surrounding neoplastic lesion of various degree and in early neoplastic foci, adenomas and carcinomas during cancer progression. On the basis of Feulgen-stained sections, alterations of nuclei were linked to the histological diagnosis of various types of liver lesions and a catalogue of potentially prognostic criteria of nuclear changes was developed. The aim of this approach is to expand diagnostic criteria, well-established in the frame of BEQUALM to nuclear changes which might help diagnosis of malignancies in doubtful cases.