This invention relates to methods of isolating cell nuclei from the other cell components in cell samples, e.g., cell samples from cell cultures or tissue samples. The method does not comprise ultracentrifugation or super-centrifugation rather the method comprises centrifuging cell samples in a table-top conventional centrifuge or microfuge. The method also comprises the use of buffers that are substantially devoid of protease inhibitor or enzyme treatments. The methods facilitate separation of nuclei from nuclear outer membranes leaving the cellular structures and inner membranes of nuclei intact. The method also provides for rapid and consistent results.