Concerning the indication to neoadjuvant treatment and its regimen, there is still a wide discrepancy in the literature. Based on the dutch TME trial, showing a low rate of local recurrence in patients treated with short-course radiotherapy (RT) compared to TME alone, the neoadjuvant therapy indication for rectal cancer was RT short-course alone. Meanwhile, with German trial publication, the indication for rectal cancer treatment, up to 15 cm from anal verge, was combination between hyperfractionated RT and 5-fluorouracil based chemotherapy (CT). Two subsequent trials (Polish trial and Trans-Tasman Radiation Oncology Group trial) showed that RT short-course alone and CRT with hyperfractionated RT have similar oncological outcomes. Thus, in recent years there has been an increasing interest in the administration of neoadjuvant chemotherapy at therapeutic doses and not only radiosensitizers. Regimens are basically as follows: induction regimen and consolidation regimen. In the first case, CT precedes pCRT, while in consolidation regimen CT follows pCRT. The rationale for this strategy is that, currently, the mortality of rectal cancer comes from distant metastases and, given that only a full dose chemotherapy can prevent the occurrence of distant recurrence, the rationale for having chemotherapy as early as possible and in as many patients is feasible (patient compliance performing adjuvant chemotherapy is low, often for complications arising from surgery). More recently, studies have been published on the use of neoadjuvant chemotherapy alone and is currently underway in the US the PROSPECT trial evaluating the possibility of using the only neoadjuvant chemotherapy in selected cases instead of the classic CRT. For many reasons (enrolment of patients in clinical trials, refusal of patients to perform treatments considered standard and toxicity from radio and/or chemotherapy) is not uncommon in clinical practice to observe patients who performed unconventional treatments and not provided by any national or international guideline.