It has been demonstrated that high frequency ultrasound (HFUS) backscatter is sensitive to the changes that occur in cells during cell death. The changes that can occur to both cell and tissue structure make the use of HFUS backscatter in vivo more difficult. Envelope statistics analysis of HFUS data can provide further information on scatterer properties and structural changes within the cells.The statistics of HFUS backscatter signals were examined by fitting several theoretical distributions. It was demonstrated that the fit parameters of the Generalized Gamma distribution can be related to effective scatterer cross section and number density for cells in suspension. These parameters also showed sensitivity to structural changes occurring in cells during cell death in vitro, with high sensitivity to changes within as few as 2.5% of the cells. It was further demonstrated that the technique can be applied in vivo to monitor the response of implanted tumours to chemotherapy.