Objectives: To estimate the incidence of acute leukemia (AL) in El Bierzo (BZ) and to carry out a cross-association analysis in order to suggest some etiological clues. Materials and Methods: We registered all new AL cases diagnosed 2000–2005. Annual standardized incidence rate (SIR) was calculated by the direct method. A cross-association analysis was performed by non-parametric methods and we checked the potential interaction between putative etiological factors by calculating Chi-square-for-trend. Results: SIR was 5.1 cases per 100 000, surpassing the Spanish, European and world average figures and heterogeneous throughout the region. We detected a negative correlation between acute myeloblastic leukemia (AML) SIR in every municipality and both the air distance to the nearest thermoelectric power plant (TPP) (Rho = –0.409; p = 0.01) and to the point of maximum density of the high-power lines (HPL) network (Rho = –0.329; p = 0.04). Accordingly, SIR was higher in the municipalities situated < 7.5 km away from TPP (9.58 vs. 1.72; p = 0.004) or < 10 km away from HPL (3.90 vs. 3.19; p = 0.045). A positive relation between both factors was observed (Chi-square-for-trend = 9.209; p = 0.006). Conclusions: SIR of AL in BZ is higher than the Spanish average and that of most countries in the world. Residing near TPP or HPL confers a higher risk of AML, with synergistic effect between both factors.