Fluorescent in situ hybridization (FISH) is a valuable tool for detection of chromosome aberrations in clinical practice of malignancies. However, the relatively high false positive and false negative rates of this method complicate its application to analysis of small populations of pathological cells. Combined simultaneous analysis of morphology and FISH using a Duet multiparametric cell scanning system (BioView, Rehovot, Israel) has been developed and introduced into clinical practice. The novel method has been demonstrated to increase the specificity of identification of pathological cells inpatients with various hematological malignancies and, hence, estimate the efficiency of treatment. Studies on different premalignant disorders of the oral cavity mucosa have demonstrated that the combined method allows the identification of individual pathological cells and, hence, early detection of malignant and premalignant cells that may be overlooked by traditional histomorphological methods.