In 1985 a report on cancer services by a Victorian Ministerial Committee, chaired by Professor RRH Lovell, recommended the  reform of the existing Peter MacCallum Cancer Institute, with the creation of a second principal cancer centre in the South Eastern Melbourne Region.

An Alfred proposal, led by Mr Ian (Cas) McInnes, Assoc. Prof. Max Schwarz and Dr John Wiseman, to build this facility at the Alfred was supported by the then-Government. This led to the hospital’s most successful building appeal in September 1987. This appeal headed by Mr John Gandel AO (Chairman) and Sir Peter Derham (Deputy Chairman) raised $5 million for the centre. The highlight of the appeal was a $1 million donation from The William Buckland Foundation, paving the way for the establishment of The William Buckland Radiotherapy Centre.

The Alfred and the Victorian Government—through the then Health Department Victoria—combined to cover the final $18 million cost and construction works took place during the early 1990s. By the time of the official "opening" on March 3, 1993, by the then Minister for Health, the Hon. Marie Tehan, the new radiation therapy unit represented the most significant development at the Alfred since the commissioning of the Main Ward Block in 1977.

Former Alfred Head of Surgery, Mr McInnes recruited Professor Alan Rodger from Edinburgh, Scotland to lead the new centre, after a global search. Professor Rodger, Head Radiation Therapist Ms Jo Smylie, and Head Physicist Mr Malcolm Millar together recruited a small team to enable the William Buckland Radiotherapy Centre to open its doors to patients in November 1992. Professor Rodger recruited Dr Sid Davis, Dr Jeremy Millar and Dr Mike Dally as consultant radiation oncologists in 1993, and the first training registrar, Dr Graham Pitson, in 1994.

The centre developed steadily in the next decade. Two more linear accelerators were installed as was a CT scanner for planning; Dr Mike Dally commenced the second stereotactic radiation program in Australia in 1996; and Dr Jeremy Millar established the brachytherapy program and introduced low dose-rate seed brachytherapy for prostate cancer to Victoria. 

Professor Alan Rodger left the Alfred in 2003 to head the Beatson, a radiation therapy centre in Glasgow. Assoc. Professor Sid Davis took over the Director's job and in the next five years led the growth of Alfred Health Radiation Oncology and in particular the building, commissioning, and opening of the Alfred Health Radiation Oncology facility at the Latrobe Regional Hospital. This was a joint venture between Latrobe Regional Hospital and Alfred Health to provide modern high-quality treatments for Gippsland patients in a centre 150km from the Alfred.