Pulmonary metastasectomy is now one of the commonest thoracic operations and is a major part of a Thoracic Department’s workload. The report by Schweiger et al. [1] in this issue of EJCTS provides a comprehensive update concerning biological and radiological markers. They note that these are not routinely used and propose that more information is needed in order to treat patients with pulmonary metastases adequately. The review from colleagues in Vienna is timely. Confidence in knowing which patients can gain benefit from pulmonary metastasectomy has been shaken by a recent analysis by colleagues from Switzerland concerning the most common application of metastasectomy in colorectal cancer [2]. The selection of patients for pulmonary metastasectomy has relied predominately on preoperative factors known to be associated with longer survival: fewer metastases, a longer elapsed time since the primary operation and raised carcinoembryonic antigen (CEA). The significance of these features has been confirmed in a meta-analysis of studies published since 2001 including 2925 patients [2]. This analysis argues for stringent selection. Based on state-of-the-art statistical methods and large numbers of patients, the metastasectomy failure (i.e. early recurrence) was seen to double for each of these three preoperative factors [2]. The Swiss analysis [2] confirms the importance of the most familiar of the biological markers, CEA. Elevated CEA nearly doubles the likelihood of failure of metastasectomy due to early recurrence [hazard ratio (HR) = 1.91, 95% confidence interval (CI) 1.57–2.32]. The principal application of serum markers is in monitoring the treatment response of cancers [3], but earlier detection is pointless unless we can use the information for patient benefit. In the early years of hepatic resection for metastases [4], a CEA assay was proposed for surveillance: its elevation triggered a ‘second-look’ laparotomy for exploration of the colonic anastomosis, lymph nodes, the retroperitoneum and mobilization of the liver with the intent of removing any further cancer discovered. Effectiveness was tested in a randomized controlled trial. Patients were randomly assigned to have CEA elevation concealed or revealed to the surgeon. Patients whose CEA elevation was not disclosed survived longer than those who had it revealed [HR = 0.85, 95% CI 0.62–1.13, not significant] [5]. It is seductive to think that the more we know about the biology of a cancer the better we can select patients for further treatment. In the hands of thoracic surgeons this further surgery is pulmonary metastasectomy. Sophisticated research is being done with this objective. Cancer biologists in Santiago de Compostela, Spain, have identified genes related to cell movement, adhesion, cell death and proliferation in circulating colorectal cancer cells [6]. From Chicago, there is a study on specific microRNAs in resected pulmonary metastases and their correlations with high and low rates of progression [7]. Casting something of a shadow on this optimism is a study from London which reports heterogeneity in different metastases from the same kidney cancer. The authors conclude that ‘heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalizedmedicine and biomarker development’ [8]. Cancer biology is already very complicated and, so far, it appears to be only at an exploratory stage. It is well short of guiding us towards better targeting of our surgical skills. Markers might lead us to identify otherwise occult cancer, but it does not automatically follow that further surgery on metastatic cancer will be of benefit. Historically each successive refinement of cancer investigation and imaging has had the effect of identifying subsets of patients that are literally beyond the reach of surgery: the disease is too diffuse or too extensive. Once that is known, these patients can be spared operations that cannot help them. In lung cancer that was the intention of the introduction of mediastinoscopy (and subsequent methods of mediastinal staging), routine computerized tomographic scanning and later, positron emission tomography. These methods are now used in the routine work up for thoracic oncological surgery and they have successively reduced the number of patients who undergo unavailing surgery. That necessarily reduces the number of operations we do, but it is undeniably a better outcome for patients than to undergo operations than cannot help and can only harm. Take the well-known example of CEA: when subjected to a randomized trial, the marker detected cancer progression, but the further surgery it prompted did not benefit the patient but unquestionably added hospitalization and suffering in their last months and years.