I had this problem (Error -50) on CD's I bought to accompany a math textbook. The publisher supplied the following helpful and very complete answer.
But first a question/comment for Apple: Many of us have video products which are incompatible with the newer versions of QuickTime. When will you fix QuickTime so it is backward compatible? Or shall we simply turn off Apple Updates forever?
Advice from textbook publisher:
Recently, Apple updated the way that QuickTime handles certain file types. Due to this, some users are experiencing difficulties viewing QuickTime content within their course or from CD-ROM. Below are the instructions to uninstall your current version of QuickTime (if you have it installed) and download and install a slightly earlier version that does work with our media files.
You must first uninstall version 7.2 of QuickTime from your computer before you try to install this 7.1.6 version of QuickTime. You do this from the Add/Remove Programs option in your Control Panel (In Windows XP go to Start Button, click Control Panel then Add/Remove Programs. In Windows Vista go to Start Button, Click Control Panel, then Programs and Features.) Once you have removed the newer version, open a browser window and go to the following URL:
http://www.apple.com/support/downloads/quicktime716forwindows.html
There is a download link that says 19.1mb and that is the file you will need to download the slightly older version of QuickTime.
Once you uninstall version 7.2 of QuickTime and get the 7.1.6 version installed, please check if your videos will play from the CD (or local hard drive.) If they do, then all is ok and you should be set. If videos do not play, follow the instructions below for recommended changes to the settings of your QuickTime.
At any point in the future if you are asked to upgrade your version of QuickTime to a newer version please don't upgrade. Upgrading to the newest version will generally give you the same problems playing videos that you had before.
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1. Open the Control Panel by clicking on your Start button and then on the Control Panel icon and click on Switch to Classic View that is on the left hand side of the window (if it says Switch to Classic View). Double-click on the blue QuickTime icon to open the QuickTime settings window.
2. Go to the Audio tab. In the Sound Out section set the Rate to: 32 kHz, the Size to: 16 bit, and the Channels to: Stereo (L R)
3. Select the Browser tab and make sure that the Play movies automatically box is checked, then click on the MIME Settings… button at the bottom. In the MIME Types window that opens, click the Use Defaults button and then click OK.
4. Select the Streaming tab and choose 512 kbps DSL/Cable in the drop-down menu under Streaming Speed. Make sure there is a checkmark next to Enable Instant-On and the indicator should be above Immediately under Play Streams.
5. Select the File Types tab and click on the Use Defaults button.
6. Select the Advanced Tab. If Transport Setup is set up to Automatic, click the down arrow in the drop-down menu and choose custom. For Transport Protocol choose HTTP, and for Port ID: 80. Click the OK button. Next, click the Empty Cache button. Under the Video section, check the Safe mode (GDI only) radio button. Click the Empty Cache button.
7. Click the Apply button on the lower right. Next, click OK. Finally, close the Control Panel.