Primary breast cancer while increasing in incidence has been successfully treated with a combination of surgery and adjuvant therapies in the majority of patients. Novel treatments for primary breast cancer need to show additional benefits to existing treatments with equivalent or improved efficacy for niche groups. Photodynamic therapy (PDT) is a potential novel treatment and a Phase I/IIA, open label, non-randomised, single site trial of photodynamic therapy for the treatment of primary breast cancer was conducted. The primary aim was to identify the light dose required for 12 mm of tumour necrosis (or a plateau of necrosis) assessed by histopathology. Post-dose MRI correlation with histopathology findings in treated tumours and in normal breast tissue was sought. In addition adverse events were recorded and comparison of outcome made with matched controls. Results of the first human clinical trial with 12 patients with median follow-up of 39 months showed PDT was well tolerated, with no adverse effects and comparable outcome to control populations. Tumour necrosis increased with incremental increases in light dose, however some patients showed a poor response even at the highest light dose. Analysis suggests that there may be predictive factors for good and poor response. PDT in primary breast cancer requires further investigation to identify which patients would most benefit from this therapy.