This paper reviews current knowledge about regulatory non-coding protein RNAs (ncRNAs) involved in the pathogenesis of chronic lymphocytic leukemia (CLL) and their potential capabilities as diagnostic markers. Diversity of clinical course as well as absence of detectable chromosomal aberrations and somatic mutations in 20 % of patients increase the interest to study the epigenetic aspects of pathogenesis. In this context, ncRNAs are believed to be promising diagnostic markers since their expression is commonly tissue-specific and they are quite stable in body fluids. Among the regulatory ncRNAs involved in the CLL pathogenesis, microRNAs and long (lncRNAs) have been most studied, whereas ring-like, or circulatory, ncRNAs (circRNAs) require further analysis. Aberrant expression of ncRNAs may account for the resistance to treatment in CLL patients without detected genomic abnormalities. Bioinformatics analysis of RNA sequencing databases allows to isolate novel candidate ncRNA molecules, including those associated with RNA-mediated suppression of the Piwi protein-interacting transposons. This paper proposes new independent predictive models based on the expression of 2 (LNC-KIA1755-4, LNC-IRF2-32-LNCRNA), 4 (miR-125b, miR-15b, miR-181c, miR-412), and 6 (PRKCQ, TRG.AS1, LNC00467, LNC01096, PCAT6, SBF2.AS1) simultaneously assessed different ncRNAs. Since risk- and stage classification of hematological malignancies is performed not only on the basis of clinical but also molecular genetic markers, the monitoring of regulatory ncRNA expression can provide an additional tool for more effective stratification of patients. The present review is concerned with the methodology issues in analytical procedures which impede widespread use of laboratory ncRNA tests.