Under-reporting of tuberculosis (TB) cases complicates disease control, hinders contact tracing and alters the accuracy of epidemiological data, including disease burden. The objective of the present study is to evaluate the proportion of unreported TB cases in Spanish healthcare facilities and to identify the associated factors. A multi-center retrospective study design was employed. The study included TB cases diagnosed in 16 facilities during 2011–2012. These cases were compared to those reported to the corresponding public health departments. Demographic, microbiological and clinical data were analyzed to determine the factors associated with unreported cases. Associated factors were analyzed on a bivariate level using the x2 test and on a multivariate level using a logistic regression. Odds ratios (OR) and 95 % confidence intervals (CI) were calculated. Of the 592 TB cases included in the study, 85 (14.4 %) were not reported. The percentage of unreported cases per healthcare center ranged from 0–45.2 %. The following variables were associated to under-reporting at a multivariate level: smear-negative TB (OR = 1.87; CI:1.07-3.28), extrapulmonary disease (OR = 2.07; CI:1.05-4.09) and retired patients (OR = 3.04; CI:1.29-7.18). A nurse case manager was present in all of the centers with 100 % reporting. The percentage of reported cases among the smear-positive cases was 9.4 % and 19.4 % (p = 0.001) among the rest of the study population. Smear-positive TB was no associated to under-reporting. It is important that TB Control Programs encourage thorough case reporting to improve disease control, contact tracing and accuracy of epidemiological data. The help from a TB nurse case manager could improve the rate of under-reporting.