Abstract: Compositions and methods for isolating nucleic acids from biological tissues and cells and for tissue/cell solubilization for other molecular biological uses, wherein the compositions comprise, in part, novel combinations of chaotropic agents and aromatic alcohols which act synergistically to effect better tissue/protein solubilization. The inventive compositions further include aprotic solvents for deactivation of ribonucleases and denaturization of proteins, as well as detergents for enhancing cell lysis and nucleoprotein dissociation. The inventive methods also comprise the use of a centrifuge, a solid-support matrix, and a microporous membrane for final isolation of the precipitated nucleic acids, resulting in high yield and purity of the precipitated nucleic acid.