Cerebrospinal fluid (CSF) surrounds the brain and spine and contains small molecules, peptides, proteins etc., which play a critical role in many physiological processes in the central nervous system (CNS). Cerebrospinal fluid is considered a privileged reservoir for neurological studies because the content of proteins and metabolites and changes in their concentrations directly reflect the internal environment of the brain: it offers a unique window for the search for new biomarkers and to improve diagnosis early onset of neurological diseases. 1-3]. However, the complexity of the human brain and neurological disorders represents a major obstacle to the identification of new neurological biomarkers. A biomarker can be defined as a biochemical, pharmacological, or physiological indicator of a specific biological state or a defined biological stage of an organism as represented in its characteristic specific specimen. Such an indicator should be measurable and possibly useful for diagnostic and/or prognostic purposes such as predicting disease progression, disease activity, and efficacy of targeted therapy. The identification of specific biomarkers is essential for the realization of personalized medicine, in terms of better estimation of disease risk, personalized therapies and improvement of disease outcome [4]. Critical to biomarker research is access to quality biospecimens that must be carefully annotated with clinical, molecular, and collection data. Indeed, sample collection must be based on well-defined protocols that provide the fundamental standard operating procedures (SOPs) for workflow certification. The National Health and Medical Research Council (NHMRC) has recognized biobanks as essential tools for biomedical research and science. It has been widely described that a large biob… half of the paper… is associated with suboptimal sample collection and storage [8, 9]. Several proteins have been proposed as an indicator of correct sample preservation. Keeping in mind all the literature to date, we review these proteins useful for quality control of cerebrospinal fluid [10-12]. We propose direct assessment of sample quality (DASQ) by applying rapid MALDI-TOF-MS methodology to evaluate the molecular characteristics of sample degradation and oxidation which have often been correlated with suboptimal pre-analytical and CSF preservation steps . This approach will provide a direct and analytical evaluation of the correct collection and storage steps of cerebrospinal fluid samples. This analysis will check for the presence of blood contamination (e.g. hemoglobin chains), truncated molecular isoforms (e.g. Cystatin C) and oxidized proteins (e.g. Transthyretin) [8, 12, 13].