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Be specific. Customize your letter for each company. Yes, it's more work that way, but you increase your chances of receiving an offer if the hiring manager senses that you didn't just do a mail merge with thirty companies and a boilerplate letter. Mention specifics from the wanted ad, indicate any history you have with the company, and/or identify any specific qualifications you possess that correlate to what the position requires.
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Do your homework. Find out exactly who you should address the letter to, and exactly how that person should be addressed (Miss? Ms.? Mrs.? Dr.? Ann?). Do some research into the company's mission, philosophy, and practices. Try to work references to this research into your letter, especially if the information coincides with your training or qualifications. Again, your extra effort should increase your chances of impressing the hiring manager and receiving an offer.
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Don't rehash your resume, but do take the chance to explain your interest in the position and/or to indicate any special relevance that your resume cannot. A short anecdote about the relevance of your experience to this particular position may be appropriate here.
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The cover letter is a good place to mention any theories, approaches, or management styles by which you are influenced.
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PROOFREAD CAREFULLY! It's a good idea to ask someone you trust to scan over your resume and cover letter as well. Nothing will get you circular-filed faster than a hard-to-read, hard-to-interpret letter, except one filled with careless errors. Employers interpret sloppy, error-filled cover letters as an indication that you are not detail-oriented or thorough.