Objective To study the role of ultracision harmonic scalpel and skin flap in axillary fossa external fixation in operation of breast cancer. Methods One hundred and sixty-six patients with breast cancer were included in this study between May 2009 and November 2009. Combined group (n=51) applied ultracision harmonic scalpel combined with skin flap external fixation. External fixation group （n=52） used the skill of skin flap external fixation. Routine group included 63 patients. Operative time, accidental injury during operation， volume of bleed and drainage, time of drainage, detection amount of lymph node, and complications such like subcutaneous fluidity were observed and recorded. Results The operative time and detection amount of lymph node were not different among three groups （Pgt;0.05）. The volume of bleed in combined group was less than that in other groups （Plt;0.05）. The volume of drainage and the time of drainage were decreased or shorten by turns from routine group, external fixation group to combined group （Plt;0.05）. The incidence rate of subcutaneous fluidity in combined group was lower than that in routine group （Plt;0.05）. Conclusions Using ultracision harmonic scalpel in operation of breast cancer can remarkably reduce the volume of bleed and drain postoperatively. Ultracision harmonic scalpel combined with skin flap external fixation is safety and can reduce the incidence rate of subcutaneous fluidity, thus can be applied widely in breast cancer operation.