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Introduction Lymphoscintigraphy with planar imaging is considered a helpful tool to depict lymph node drainage in patients with invasive breast cancer. Single Photon Emission Computed Tomography with integrated CT (SPECT/CT) is usually performed to detect sentinel nodes (SN)s in breast cancer patients showing non-visualisation on lymphoscintigraphy. Incorporation of new SN indications (recurrent surgery, previous radiotherapy, or neo-adjuvant chemotherapy) has led to an increase of non-visualisation rates. The present study evaluates the contribution of SPECT/CT and tracer reinjection for SN-visualisation in breast cancer patients without drainage on lymphoscintigraphy. Methods Between 1st of July 2008 and 6th of November 2014 in total 1968 patients underwent a SN breast procedure, using intra-tumoural tracer administration. SPECT/CT was performed in 284 breast cancer patients with non-visualisation of SNs on lymphoscintigraphy. If SN non-visualisation persisted, a second radiotracer injection with repeated imaging was performed when logistics allowed this. Univariate analysis was applied to evaluate SPECT/CT visualisation rates in specific subgroups. Results The SPECT/CT visualisation rate was 23.2% (66/284). Univariate analysis revealed no significant subgroups influencing SPECT/CT visualisation. In patients receiving reinjection after persistent SPECT/CT non-visualisation the SN-visualisation rate reached 62.1% (36/58). Intraoperatively, the SN-identification rate using a gamma probe and blue dye was 87.9% (175/199) and 32.9% (28/85) for, respectively, primary and recurrent surgery after non-visualisation on lymphoscintigraphy. Conclusion In this evaluation including new breast cancer SN indications, SPECT/CT scored lower than reinjection to visualise SNs in patients with non-visualisation on lymphoscintigraphy. Consequently, our institutional protocol has been readjusted. [ABSTRACT FROM AUTHOR]