The distribution of certain elements, which in higher content represents hazard to the environment, causes certain unwanted consequences on human health. Therefore, the environmental monitoring not only for the lithogenic but also for the anthropogenic distribution leads to determination of the main hot spots in environment. The anthropogenic activities for exploitation of natural resources and their processing represent a global problem of pollution of the environment. Bregalnica River Basin in the Republic of Macedonia was selected as a study area with the presence of three potential emission sources: lead and zinc mines (“Zletovo” and “Sasa” mines) and copper mine (Bučim mine). Lithogenic and anthropogenic distribution of 69 elements (Ag, As, Al, Au, B, Ba, Be, Bi, Br, Ca, Cd, Ce, Co, Cr, Cs, Cu, Dy, Er, Eu, Fe, Ga, Gd, Ge, Hf, Hg, Ho, I, In, Ir, K, La, Li, Lu, Mg, Mn, Mo, Na, Nb, Nd, Ni, Os, P, Pb, Pd, Pr, Pt, Rb, Re, Rh, Ru, Sb, Sc, Se, Sm, Sn, Sr, Ta, Tb, Te, Ti, Th, Tl, Tm, V, W, Y, Yb, Zn and Zr) was evaluated in river water, sediment and alluvial and automorphic soil from Bregalnica River Basin in the Eastern part of the Republic of Macedonia. The monitoring was conducted in the period of 2012-2013. Determination of the total elements contents was performed using mass spectrometry with inductively coupled plasma (ICP-MS) and atomic emission spectrometry with inductively coupled plasma (ICP-AES). The obtained values for the contents of certain potentially toxic elements show significantly higher values in all types of samples taken from the vicinity of the mines. The geochemical associations F1 (Ca, K, Mg, Na, Ba, Li, Mn, Sr, V); F2 (Al, Fe) and F3 (Sb), were the basic lithogenic markers for the elements distribution in river`s water, with insignificant variations. Distribution of the anthropogenic chemical association (As, W, Ba, Ag, Cu, Tl, Zn, Sb, Mo, In, Cd, Te, Bi, Pb) in the sediments, dominate in the Pb-Zn deposits (“Sasa” and “Zletovo” mines), characterized with anthropogenic impacts. Soil analysis indicates that the lithogenic distribution is represented by the following factors: F1 (Ti, Eu-Lu, Y, Fe, Sc, V, Nb, Co, La-Gd, Ga, Ge, Cu), F3 (Rb, K, W, Ba, Ta, Tl), F4 (Zr, Hf, Br, Pd, Sr, As), F5 (Ni, Cr, Mg) and F6 (B, Na). The anthropogenic distribution represents the factor F2 (Cu, Pb, Sb, Cd, Sn, Zn, Te), where the regions of mines cover 90 percentile of the contents of these elements.