Polymorphisms in genes coding xenobiotic‐metabolizing enzymes are considered as risk factors modifying susceptibility to cancer. We developed a biochip for the analysis of 18 mutations in 10 genes of metabolizing system: CYP1A1, CYP2D6, GSTT1, GSTM1, MTHFR, MTRR, NQO1, CYP2C9, CYP2C19, and NAT2. Using allele‐specific hybridization on the biochip 76 T‐cell non‐Hodgkin's lymphoma (NHL) patients, 83 B‐cell chronic lymphocytic leukemia (B‐CLL) patients, and 177 healthy donors were tested. Polymorphic CYP1A1 alleles were more frequent in B‐CLL patients relative to normal controls, for example, a combination of polymorphic variants 4887C > A, 4889A > G, and 6235T > C (OR = 1.76, 95% CI = 1.0–3.1). The GSTM1 null genotype was more frequent in NHL patients relative to controls (OR = 1.82, 95% CI = 1.1–3.1). The combination of unfavorable polymorphic CYP1A1 variants and GSTM1 null genotype was found more frequently in B‐CLL patients relative to controls (OR = 2.52, 95% CI = 1.3–4.9). In addition, male B‐CLL patients demonstrated a significantly increased occurrence of heterozygous and homozygous allele *2 of CYP2C9 gene (OR = 2.38, 95% CI = 1.1–5.2) as well as a combination of alleles *2 and *3 of the gene (OR = 2.09, 95% CI = 1.1–3.9). Thus, our findings show the association between polymorphic alleles of CYP1A1, GSTM1, and CYP2C9 genes and the risk to develop NHL or B‐CLL. The developed biochip can be considered as a convenient analytical tool for research studies and predictive analysis in oncohematology. Am. J. Hematol., 2008.