The present study summarizes the last ten years of literature on heavy metal distribution in Suspended Particulate Matter (SPM) and dissolved phase in the Po River (Italy). The work compares different methodologies employed to collect, concentrate and fractionate the samples. The importance of metal speciation as a function of particle size is underlined and two approaches to metal speciation in the colloidal fraction of Po River SPM are presented: Sedimentation Field-Flow Fractionation (SdFFF) and pH-dependent extractions. Finally, emphasis is placed on the need for comparison with a reference "natural background level" of the metal load in Po River particulate matter in order to determine the real human contribution to river pollution. The high values of some trace transition elements, such as Cr and Ni, have been compared with clay sediments around Ferrara and with bricks in historic buildings. The highly comparable natural concentration of these metals in Po fine sedimentary rocks and in historic brick buildings of Ferrara (XII-XVI centuries) can provide information on natural geochemical anomalies.