Welcome to the first issue of Nature Reviews Cancer for 2014 and happy New Year to you!

First, we would like to thank all of last year's authors for writing for us and all of last year's referees for helping us to continue to publish outstanding Review and Perspective articles. Your time is very much appreciated.

Second, as it is a new year, we are starting with something new: a special series of Comment articles with clinical roots. It is easy to get caught up in the finer details of cancer biology and to forget the real end point of all our efforts: the effective treatment of cancer patients. Clinical studies teach us a great deal about the processes and mechanisms underlying cancer, and they also reveal to us and remind us of aspects of cancer that we still do not understand.

Children with neuroblastoma are a case in point. The outcome for children with metastatic neuroblastoma heavily depends on their age and the characteristics of their tumour. Indeed, for some very young children who are diagnosed with metastatic special disease (MS; previously known as stage 4S) the prognosis is very good because this type of disease is characterized by spontaneous regression. If we could understand how and why this regression occurs, we might understand more about the molecular biology of metastasis and tumour regression.

Patients receiving therapy do not uniformly respond to cancer treatments: some exhibit resistance from the start, a concept with which we are all familiar, but others undergo exceptional responses for reasons that are often not understood. Undoubtedly, all of these examples might well have something to do with how the cancer has evolved within the individual. Indeed, why has a cancer arisen in a particular person, and is cancer much more common than we think? Can early tumours evolve down evolutionary 'dead ends' and thus have no clinical impact? And is this what happens in the majority of people who are not diagnosed with cancer?

Many of these scenarios highlight patients who could be considered outliers, but, as we are discovering in other areas of cancer research, perhaps we should pay more attention to these outliers. In recognition of this, we have commissioned a series of Clinical Insight Comment articles that address several thought-provoking observations from the clinic. Hopefully, thinking about these more unusual and often overlooked aspects of cancer might help us to overcome some of the current stumbling blocks in cancer research.