**1. Introduction**

Cancer metastasization is a highly selective, sequential, interdependent, nonrandom process which causes transient or permanent changes in different genes at the DNA and/or mRNA, creating a complex phenotype which favors the survival of a population of tumor cells within an organ environment, distant from the primary tumor [1, 2]. This kind of complex process usually requires many years in order to complete the great series of cumulative DNA changes which consent neoplastic cells to metastasize. As the primary tumor growth may be very slow and the metastasization process does not directly depend on primary tumor size, we can observe two kinds of metastases based on the timing of their diagnosis: synchronous metastases are defined as secondary lesions diagnosed within the first year after primary tumor diagnosis, although this time, interval may vary in the literature between six months and one year, while metachronous metastases are usually diagnosed after one year from the primary tumor diagnosis.

Taking into consideration all primary tumors, the liver represents the most common site of the distant metastases. This particular affinity for distant metastases may have different explanations. First, it may be attributable to the site specificity patterns of neoplastic cells from various primary cancers, which found the liver as the adequate soil where to seed their circulating neoplastic cells [3, 4]. Furthermore, the liver receives 30% of the whole cardiac output, second only to the kidney for the quantity of blood which every day will perfuse its parenchyma, and is consequently more susceptible to neoplastic cell attachment. Moreover, anatomical or mechanical considerations, such as the efferent venous blood stream or the loco-regional lymphatic drainage, may be strongly responsible for this preference in the metastasization site [5]. In fact, most intra-abdominal cancers, and in particular those which originated in the digestive tract, result in having a great affinity for liver metastasization.

In spite of the great progresses of surgical techniques against the primary tumors, as well as the improvement of adjuvant therapies, metastatic disease continues to be the greatest challenge for the medical and the surgical oncologists. In fact, metastases are well recognized as being the major cause of death among neoplastic patients, and the prognosis of patients affected by unresectable liver metastases is very poor. However, although once metastatic malignancies were commonly considered as a terminal neoplastic stage, nowadays, many different therapeutical options have been introduced in order to provide a safe and efficient treatment for these kinds of patients and improve both their quantity and quality of life [6–9].

Despite the abundant literature about colorectal liver metastases and the existence of a great number of guidelines about this argument, there is still great debate about the treatment strategy in the case of non-colorectal ones and controversies especially about the management of rare liver secondaries. On the other hand, a recent review about non-colorectal non-neuroendocrine liver metastases demonstrated surgery to be a benefit for these kinds of metastatic patients, especially for those affected by primary testicular, ovarian, and renal cell cancers but also for women with isolated breast cancer metastases to the liver [10].

Obviously, patients affected by rare hepatic metastases should be conveyed into bigger and more experienced centers, which could be able to more appropriately treat this kind of disease. However, metastatic patients are always more numerous – thanks to the improvement of chemotherapy and the introduction of targeted biological drugs – and deserve as many chances of treatment as possible in order to continue their long battle against cancer. In this chapter, we will then discuss indications and timing of surgery in cases of the most frequent non-colorectal liver metastases.
